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Sturgeon's House

Biotechnology and Bioengineering Thread


Toxn

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I suspect the Chinese will put this sort of thing into practice first, just because the Anglos don't want to seem like they are doing eugenics.

Nothing eugenic about it in principle, but yeah. The anglosphere seems to be in the process of rolling back or banning anything to do with biotech. 

 

My suspicion is that, as these advances accumulate, they will become more and more attractive to countries who worry about agricultural productivity and population growth (ie: China). China already has is currently building the world's largest animal cloning facility, so I also expect that there will be more and more local expertise available over time to push into artificial human reproduction.

 

Edit: some clarity edits. Also, the level of fear mongering when you search for news stories about Tianjin is hilarious.

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  • 2 weeks later...

Since this was announced today, I thought it might be a good time to look at other useful mods to give to your children:

  1. If the mitochondrial free radical theory of aging is correct (or even if it is incorrect but less leaky mitochondria produce a health benefit without increasing lifespan), then doing something drastic like introducing avian mitochondria might be a good idea. This has all sorts of associated issues in terms of co-evolution of mitochondria and hosts, but would still be an interesting thing to test.
  2. If the telomere theory of aging is correct, then upping telomerase is an obvious candidate for improving lifespan/health.
  3. Mod in HMM-HA. This seems like an easy fix (single gene insertion) and would be pretty easy to test in terms of improved health outcomes.
  4. Mod in a functional version of gulonolactone oxidase. Because, really, who needs the hassle of scurvy even as a theoretical possibility?

There are a bunch of others which would be useful in certain contexts (more melanin for us whiteys who get too much sun, myostatin mutants, HIV resistance and so on) but these are a bit more situational.

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I've got a class mate who's doing research with engineering plants that create human proteins. 

 

I asked him how he deals with chaperone folding and glycosylation. He told me that's a real issue, and that they currently have been able to get just the glycosylation on a single protein. 

 

But he swears that he can outperform CHO cells in all bio reactors AND cost AND time AND protein purity. 

 

Plus, he stated that since it's plant derived, you wouldn't have to make it subject to viral or serious impurity tests because plant diseases can't jump to humans.

 

Classic academic thought process. Try explaining that to the FDA when you don't run through their prescribed testing protocol.  

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It seems that DARPA is/was investigating implanting small devices into insects in order to make surveillance devices out of them.

 

Interestingly, the documents mentioned refer to William's experiments, which seriously sparked my interest in biology when reading about them as a child. I immediately recognised the exact photo used in the DARPA presentations.

 

This eventually formed the basis for my long-running idea of using filling a pre-made exoskeleton (with or without supplementary electronic/mechanical devices) with tissue cultures in order to create a complete animat.

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I've got a class mate who's doing research with engineering plants that create human proteins. 

 

I asked him how he deals with chaperone folding and glycosylation. He told me that's a real issue, and that they currently have been able to get just the glycosylation on a single protein. 

 

But he swears that he can outperform CHO cells in all bio reactors AND cost AND time AND protein purity. 

 

Plus, he stated that since it's plant derived, you wouldn't have to make it subject to viral or serious impurity tests because plant diseases can't jump to humans.

 

Classic academic thought process. Try explaining that to the FDA when you don't run through their prescribed testing protocol.  

Freaking post-translational mods - the bane of protein production everywhere.

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  • 1 month later...

It's a really clever solution, so long as the damn things don't pick up exogenous DNA from the environment. My bet is that we'll see a lot more cool mods like this as sequencing and synthesis both bottom out in price.

Microbiology is pretty much the wild frontier of genetic engineering right now, not least because it's the area of biotech with the least onerous regulation. This is something that gives me a bit of bitter satisfaction, given how said regulations are sold in terms of managing risk and how bacteria are, you know, tiny and fucking everywhere.

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I'll add to Toxn's post. 

 

The issue with most genetically modified bacteria treatments is that FDA regulations here in the states require clinical trial recipients at all stages to come away from the treatment unchanged from when they entered. This means that whatever thing that was pumped into them, whether it be protein, bacterium, DNA, etc, must be provably nonexistent in their body at the end of the trial. 

 

For instance, a group of geneticists reprogrammed the most comment cavity-causing bacterium to produce ethanol instead of lactic acid during its metabolism of pyruvates. This was as simple as switching a single enzyme. 

 

However, once that bacteria takes hold in your mouth, you can't really get rid of it. Thus, they couldn't even begin phase one clinical trials. 

 

I like that the Duke team implemented apoptosis to their bacteria. My hope is that their calculations for diffusion and regulation of those apoptotic markers coincide with the death of the gliomas. 

 

Also, I'm wondering how they are getting the salmonella to divide quickly in a low oxygen environment. To my knowledge, Salmonella doesn't do that well anaerobically. And the byproducts wouldn't be good for a brain, but that's probably been seen to by the team. 

 

All in all, I'm highly pro genetically engineered bacteria. It's a beautiful and burgeoning field that deserves less FDA intervention (or at least a revision of FDA rules to account for the new science) and more bright minds. 

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Adding to this: bacteria are where we are the closest to doing real engineering (as opposed to tinkering), given that we have lots of tools for modifying and testing bacteria and have enough synthesis capability to make a (small) bacterial genome from scratch.

 

The way I see the field going in the next few decades, it should become pretty common to start a project, haul out a minimal bacterial genome, add in your pathways using standardised biological parts, optimise in silico, order your genome synthesised and then drop it into an empty donor. This would allow you to build novel bacteria from the ground up to do specific tasks*.

 

The problem is that, as Oedipus mentions, you then have some pretty difficult limits on what you can do with your new bacterium once you've made it. This is sort of a good thing from a precautionary principle standpoint, but is very much akin to having the tech to make cellphones but then having to submit every new model for laborious testing to make absolutely sure that it won't cause cancer or something before you can release it. And microbial biotech is actually very un-regulated compared to something like GMO plants!

 

I often fantasize about someone buying an uninhabited island and turning it into a rules-free zone for biotech development and testing, specifically because of how painfully slow and in-innovative our current approach is.

 

 

* A few examples of stuff we could get bacteria to do pretty easily: make a huge number of organic compounds (including polymers and various drugs) using nothing but agricultural waste as feedstock, make biofuels, act as components in biological circuits (including bio-batteries and bio-computers), act as exquisitely sensitive and cheap chemical sensors, act pretty much as nanobots for disease applications (as seen in the example above) and act as novel beneficiation systems for things like mining (ie: concentrating specific chemicals in ore and/or converting them to a useable form). 

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I'll add to Toxn's post. 

 

The issue with most genetically modified bacteria treatments is that FDA regulations here in the states require clinical trial recipients at all stages to come away from the treatment unchanged from when they entered. This means that whatever thing that was pumped into them, whether it be protein, bacterium, DNA, etc, must be provably nonexistent in their body at the end of the trial. 

 

For instance, a group of geneticists reprogrammed the most comment cavity-causing bacterium to produce ethanol instead of lactic acid during its metabolism of pyruvates. This was as simple as switching a single enzyme. 

 

However, once that bacteria takes hold in your mouth, you can't really get rid of it. Thus, they couldn't even begin phase one clinical trials. 

 

I like that the Duke team implemented apoptosis to their bacteria. My hope is that their calculations for diffusion and regulation of those apoptotic markers coincide with the death of the gliomas. 

 

Also, I'm wondering how they are getting the salmonella to divide quickly in a low oxygen environment. To my knowledge, Salmonella doesn't do that well anaerobically. And the byproducts wouldn't be good for a brain, but that's probably been seen to by the team. 

 

All in all, I'm highly pro genetically engineered bacteria. It's a beautiful and burgeoning field that deserves less FDA intervention (or at least a revision of FDA rules to account for the new science) and more bright minds. 

Asking for a friend; is a sample of the transformed bacteria being kept on ice somewhere? Would it be possible to export it for testing overseas?

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Asking for a friend; is a sample of the transformed bacteria being kept on ice somewhere? Would it be possible to export it for testing overseas?

I'll have to check which bacteria it is, but it's a simple enzyme replacement. Just cut out the code for Lactate dehydrogenase and push in the code for alcohol dehydronase. 

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  • 2 weeks later...

Time for a ranting about PhD friend.

 

So my Senior Design Project has begun. I should post about ti, to explain it in detail, but here is the overview. 

 

A waste water stream from a film production plant changes composition daily. This composition consists of about a thousand chemicals. Each day it goes through a continuous process to remove silver, cause that shit's expensive. My project is focused on the silver removal process. Bromide concentrations at this stage in the treatment are highest, and Bromide has been shown to negatively affect the reproduction of certain indicator species in rivers. 

 

The EPA has no set standards for Bromide in waste streams, so research was conducted and we have a target concentration of Bromide we wish to achieve. 

 

Our job is to find a way to remove the Bromide from the continuous process of Ag removal. 

 

Now, there's some decent reasons to focus on the silver reclamation part of the process. 

 

1) The concentration is highest here. 

2) It's a continuous process.

3) It has the lowest flow rate (At ~100 Gallons per minute)

 

Now here's where the story gets fun. I'm having a beer with my buddy, a bio PhD, and explaining the situation. 

 

He hits me with, "Could you find a bacteria that removes the bromide?"

 

"And turns it into what? Also, if you can find a bacteria that can live in a rapidly changing ecosystem consisting of about a thousand nasty chemicals in quite turbid water that also has to go through sand filtration AND carbon filtration for arsenic levels, let me know."

 

"Well why not just treat it after that step?"

 

"What? In the waste water clarifying ponds next to the facility?"

 

"Sure! Just set up a bacterial strain there and have them take the bromide out for you."

 

At this point, I'm looking at him sideways. "So you think you can keep a bio-reactor running, in the elements, that has a flow rate of over 15,000 gallons per minute, with numerous different compositions coming in that change daily? Are you mad?" 

 

And yes, the final ponds receive a ton of extra flowrates from different process and treatment facilities. 

 

He goes on, "Well, yeah, why can't you make that work?" 

 

At this point he's staring at me like I'm the crazy dumb one. 

 

So I say, "Tell you what, you go ahead and do the calculations on Halide transport across cellular membranes at those concentrations, because I'm sure you understand that the driving force for that transfer is concentration gradients, and you get back to me on how well it'll work out for your hypothetical bacteria that doesn't exist yet. 

 

"Well, you could just create the bacteria and give it the genes to get Bromide out of the water-"

 

"So now you're trying to introduce a non-native, genetically altered species into the river system? And you don't think the EPA won't have anything to say about that?" 

 

He went back to his beer, mumbling about how he's sure I could get something like that to work if I just tried hard enough.

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Time for a ranting about PhD friend.

 

So my Senior Design Project has begun. I should post about ti, to explain it in detail, but here is the overview. 

 

A waste water stream from a film production plant changes composition daily. This composition consists of about a thousand chemicals. Each day it goes through a continuous process to remove silver, cause that shit's expensive. My project is focused on the silver removal process. Bromide concentrations at this stage in the treatment are highest, and Bromide has been shown to negatively affect the reproduction of certain indicator species in rivers. 

 

The EPA has no set standards for Bromide in waste streams, so research was conducted and we have a target concentration of Bromide we wish to achieve. 

 

Our job is to find a way to remove the Bromide from the continuous process of Ag removal. 

 

Now, there's some decent reasons to focus on the silver reclamation part of the process. 

 

1) The concentration is highest here. 

2) It's a continuous process.

3) It has the lowest flow rate (At ~100 Gallons per minute)

 

Now here's where the story gets fun. I'm having a beer with my buddy, a bio PhD, and explaining the situation. 

 

He hits me with, "Could you find a bacteria that removes the bromide?"

 

"And turns it into what? Also, if you can find a bacteria that can live in a rapidly changing ecosystem consisting of about a thousand nasty chemicals in quite turbid water that also has to go through sand filtration AND carbon filtration for arsenic levels, let me know."

 

"Well why not just treat it after that step?"

 

"What? In the waste water clarifying ponds next to the facility?"

 

"Sure! Just set up a bacterial strain there and have them take the bromide out for you."

 

At this point, I'm looking at him sideways. "So you think you can keep a bio-reactor running, in the elements, that has a flow rate of over 15,000 gallons per minute, with numerous different compositions coming in that change daily? Are you mad?" 

 

And yes, the final ponds receive a ton of extra flowrates from different process and treatment facilities. 

 

He goes on, "Well, yeah, why can't you make that work?" 

 

At this point he's staring at me like I'm the crazy dumb one. 

 

So I say, "Tell you what, you go ahead and do the calculations on Halide transport across cellular membranes at those concentrations, because I'm sure you understand that the driving force for that transfer is concentration gradients, and you get back to me on how well it'll work out for your hypothetical bacteria that doesn't exist yet. 

 

"Well, you could just create the bacteria and give it the genes to get Bromide out of the water-"

 

"So now you're trying to introduce a non-native, genetically altered species into the river system? And you don't think the EPA won't have anything to say about that?" 

 

He went back to his beer, mumbling about how he's sure I could get something like that to work if I just tried hard enough.

I've explained to people (usually engineers) that one of the problems with biotech is that enzymes are just so damn good at what they do.

 

"Hey look; there's this thing floating about that can catalyze a reaction with amazing specificity and speed, runs at STP and can be produced at scale using nothing more than sugar and a spoonful of goop to start the process off with."

 

"Oh wow, lets use it to bleach paper!"

 

We are literally surrounded by self-replicating nanotech which allows us, with the barest minimum of knowledge, to do things that would make a chemist cry tears of frustrated longing into his three headed distillation column. And unfortunately this encourages magical thinking.

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