a note on genetic engineering

[imachavel]

whoa, that last thread got bombed to death(not insultingly so), people seem to disagree with a presented idea already accepted as being not possible, which would lead science nowhere if people all thought like that, NONE THE LESS

I was trying to ask a question on the advancement of genetic engineering. I'm not just talking about natural lsd

in the 1800's I don't think people could have imagined synthetically creating so many drugs in a laboratory, I was trying to say

IN THE FUTURE OR SOMEWHAT

do people see there being all types of new 'designer plants?'

I'll bet in the year 2500 or some crap or another there'll be all types of new plants instead of just 'designer drugs'

right???

ehhhhhh?????

yeaaahhhh... I CAN'T WAIT to get high in the future......




on another note: I still get the feeling there's some advanced evolution causing reaction in genes or something that could be amplified that no one's discovered. Think of the genetic changes in cannabis discovered over the years. But I'll bet cannabis was always that easy to change, we can just control the environment better now. I believe one day there'll be some discovery posing the possibility of enhancing evolution by enhancing genetic change with plants in different conditions, winter palm trees, plants accepting poisons and using them as biomolecules, stuff like that! who knows what hell is possible! ehhhh? yeah!!! I can't wait to get high in the future!!!!! !!!!!!!

 

[benzyme]

these things (genetic expression in new hosts via transformation) are possible today, in limited applications.

what you were talking about, influencing plants to produce LSD-25 (as in the 25th compound in a sequence of lysergic compounds) is not one of those.
what's more practical is influencing metabolism (possibly through manipulating ergot itself) to increase ergotamine yields, this may also be done through transformation.

 

[deedle-doo]

A lot of this kind of work is going on. I think it is a mostly unsavory form of manipulation because it has the potential of radically altering the planets ecology.
Another unsavory aspect of this work is that it is mostly being done by multinational corporations. Monsanto owns food plant genomes and keeps 'em secret. The big ideas are to make fuel crops that can grow in arid environments and to make hardy rice or maize that has a full complement of amino acids and vitamins. Worthy goals but at what risk.

IMO engineering plants to be hardy to extreme conditions and/or resistant to predation is a BAD IDEA. (Bear in mind that I say this from a western, well-fed ivory tower.) We cannot really predict the long term ecological impact of sowing large tracts with such plants. Until we can accurately model that kind of thing we should probably just keep talking about it.

But it is happening and you might have already eaten it. The biggest money maker in this arena so far has been 'round-up ready' crops. I forget the biochem but apparently you can make corn resistant to round-up (which generally kills all grassy plants.) This has been done and the seeds are out there.

Genetic engineering has been and will be used to produce valuable pharmaceuticals, including small molecules like the ones we know and love. However, don't picture apples or honeysucles filled with insulin or DMT. Picture 1,000L vats of brewing yeast. This is what it will look like.

Yeast is the only platform where you can express enzymes in a determined order at specific molar ratios with some ease. This still will take years and 10s-100s of thousands american dollars for each small molecule target. Especially right now.

The market will ultimately decide this kind of applied research. Generally I bet such genetic synthesis routes will only be employed for strange, exotic, complex molecules for which standard synthesis is not commercially feasible. Unless there is a major shift in western societies' attitude toward altered states I cannot see the force of the market pushing for such a product in the near future.

If psychedelics were made legal and socially acceptable I think our pharmacopia would stay the same but we would be sold products to enhance the experience. Hotel rooms and amusement parks and television programming etc. made specifically to enhance a psychedelic experience.

Anyway, if you want to know more about this kind of science you should focus your studies on modern biology and chemistry. Build a solid foundation of molecular genetics and enzyme reaction mechanisms. Then start to read about 'metabolic engineering'.

 

[deedle-doo]

on another note: I still get the feeling there's some advanced evolution causing reaction in genes or something that could be amplified that no one's discovered.

Yes but this was discovered millennia ago when our ancestors started cultivating softer and softer grains and nicer and nicer goaties. Domestication and selection works. It is possible because wild populations of any critter harbors unseen genetic diversity that is only revealed by strong selection. This is how lineages survive such a hostile and unstable earth.

 

[imachavel]

yes, I see what you're saying. But the thing is, most of genetic engineering is based on taking genes from another source and splicing them, no one's cracked open the ability to just enhance the genes that are there yet, right? or if so to an EXTREMELY LIMITED extent.

take for example an lsd producing plant, it would have to be a shade plant, so to get some type of plant you'd splice a hawaiian baby woodrose gene with a plant that grows in the shade to get the genetics of both, right? but that's it, unless you had the enzyme to convert lysergic acid to lysergic acid diethylamide implanted in the genes already.

but if you could TAKE the genes OF a hawaiian baby woodrose, and could manipulate them to do what you wanted, you could get it to grow in the shade, and probably enhance it to NEED lsd which is just a fairy tale since the molecule is so unstable and no one knows a genetic use for it for any plant.

anyway, that whole lsd thing is aside from the point. I guess what I'm saying is who knows what people could do with science, build some crazy machine, put plant cells in there, alter their genetic evolution with some micro camera analyzer and the process in which to do so. I mean it sounds beyond us I suppose, I'm just suprised to think with all the advancements in the 20th century from the 19th century and all the 'designer drugs' that there won't be 'designer plants' in this century or the next, not just lsd, but whatever.

although I guess that's useless, but so are designer drugs for the most part. in the 19th century, if people could have 'guessed' the ability to synthesize so many chemicals, they would've said it was impossible, OR they would've said it's useless to design things like lsd or dmt or 2-ci or mdma in a laboratory, but shit we did all of that. Think of how insane splitting an atom would've sounded.

but your right, splitting an atom is easier than this stuff, so it has some boundaries, still though, there's so much shit we probably don't know. Stanley Miller's experiments probably seem simple and a basic thing we didn't know about that he could take a simple reaction and produce amino acids. But who knows, maybe that's a breakthrough, producing amino acids is just a step, maybe there's some reaction that takes place when dna is changed that can be scientifically produced easily. Maybe the next stanley miller will have some type of reaction that produces dna FROM amino acids. I mean, I don't know.

sounds hard to believe, right? producing genetic changes in dna takes millions of years, but doesn't creating amino acids from an electrical gas experiment also? doesn't it? I don't know, that's why I'm asking.

 

[deedle-doo]

anyway, that whole lsd thing is aside from the point. I guess what I'm saying is who knows what people could do with science, build some crazy machine, put plant cells in there, alter their genetic evolution with some micro camera analyzer and the process in which to do so. I mean it sounds beyond us I suppose, I'm just suprised to think with all the advancements in the 20th century from the 19th century and all the 'designer drugs' that there won't be 'designer plants' in this century or the next, not just lsd, but whatever.

You are absolutely correct. There will be designer plants in this century. There are already. There are several robust technologies for introducing genes into a few plant species. Read about Arabidopsis thaliana. Some pretty amazing science is going on there.

 

[deedle-doo]

but if you could TAKE the genes OF a hawaiian baby woodrose, and could manipulate them to do what you wanted, you could get it to grow in the shade, and probably enhance it to NEED lsd which is just a fairy tale since the molecule is so unstable and no one knows a genetic use for it for any plant.

Remember a basic rule of genetics. One gene = One enzyme.
Like all basic biological rules this one is only mostly true But for metabolic genetics (which is what you want to learn about) it is good enough. Small molecules are built up by a host of enzymes that each add or remove or change some molecule. These operate in pathways that pass along intermediates from one enzyme to the next. These pathways are ruled by flux rules that are fairly easy to comprehend with discipline. If you can understand the reaction mechanisms of enough enzymes you can construct a small molecule. Assuming you can reliably express enzymes in a controlled molar ratio and extract intermediates that can be re-fed to your culture.

I think we'll definitely be hearing about this more in the future. Companies are performing mass sequencing all over the world to discover new enzymes that catalyze very specific reactions. Some very cool ones have been found in sponges and their microbial symbionts. I imagine the diversity of life on earth may have generated enough enymes for almost anything we'd need.

You also bring up the notion of custom proteins. These are the nanomachines. We will be able to interact with matter on a magically fine scale. Systems biology + protein folding/structure/function will provide us with functional pathways to a great deal of ends, including small molecule synthesis. Imagine a computer program that would spit out a series of genes that could be used to construct any molecule from a given starting material in a great slurry of molecule excreting yeast. Imagine reactors filled with these cultures constantly fed with glucose and metabolites and oozing product into some kind of collection contraption.

This kind of technology will also yield fantastic materials of the future. Like super low friction surfaces and super small microchips, etc.

But research is slow. Systems biology and computational design of metabolic pathways are pretty cutting edge stuff. The protein folding/design problem is almost a holy grail to modern biology. It has eluded humanity since the discovery that proteins have ordered shapes in the last century. Maybe it could be you, in your mad quest for psychedelic tomatoes, who will make a breakthrough
Look into it. These fields are fascinating and wide open.

 

[deedle-doo]

sounds hard to believe, right? producing genetic changes in dna takes millions of years, but doesn't creating amino acids from an electrical gas experiment also? doesn't it? I don't know, that's why I'm asking.

Nah. Changes in DNA happen all the time. This is what will kill many of us at some point. It only takes a second for DNA to change but the chance of that change being good is very very small.

 

[imachavel]

damn, that's fucking interesting

thank you, that was one of the best replies I've ever had.

 

[burnt]

people are currently using metabolic engineering to make plant cell cultures to increase secondary metabolite production. also using random genetic mutation to create novel compounds. i think this is a useful technology, it will allow certain drugs to hopefully one day be produced cheaper and easier with less synthetic and or isolation procedures. its not easy though, much more research needs to be done. it wouldn't be useful for a drug like lsd though because its relatively easy to make and making the fungus produce excess ergotamine would be much easier as mentioned already.

look up the drug taxol. look at that structure for a minute. its no joke to synthesize that! that cancer drug is very useful and found in only small amounts in the pacific yew tree. so rather then destroy a bunch of trees or utilize a very complicated synthesis method, people are trying to produce it in plant cell culture and even transferring the entire biosynthetic pathway into e. coli. this is a useful application of this technology. but it took tons of money and research to even small increases in yield but at the same time more is being learned about the fundamentals of genetic and metabolic regulation, which needs to be better understood to get this technology going better.


as far as genetically engineering food crops, screw monstanto there going to mess it all up. but yes although i think we need to be very very careful. i think in some cases some very useful things will come out of it. but in order for genetic engineering to work in agriculture we need to first go back to using more organic farming and permaculture practices on more local scales. combine that with a minimal amount of genetic engineering only when necessary and chemical pesticides only when necessary and we will solve food problems worldwide. mono-culture massive industrial agriculture needs to change to something with more long term sustainability.

 

[imachavel]

I thought biosynthetic taxol production had been achieved already.

anyway, that's true, now at this time these things aren't advanced. But in the future, who knows, maybe EVERY person with a science degree will be altering plants.

I don't know, it seems interesting to me, who knows what they might develop, maybe there'll be some albert hoffman in the future who learns an enzyme to produce a psychedelic in some plant while experimenting with enzymes to find heart medicines, it could be the next big undiscovered psychedelic.

right now genetic engineering is very new, but who knows what microtechnology they can achieve, maybe one day synthesizing a proten will be like playing with a shaping device on a computer, entering the new molecule you want to experiment with, then adding it into the system, and letting some machine take a day to fold all the proteins to see if an enzyme is possible to create this molecule, coming back in the morning, and seeing 'what's in the microwave'

it could be like that someday, real george jetson shit. Or maybe there'll be some super evolutionary synthesizer, they put plant cells in a machine, grow plants and see what new genetically evolved specimens come out.

right now this is all a dream, but I know a computer was something probably never even thought up at one point in human history. Imagine how impossible people must have thought a computer was in the year 1000, you'd have thousands of people saying it can't exist and crap.

look at it like this, there's some things we almost certainly can't synthesize in a plant, what they are? right now, who knows. But there's some reactions that just CAN'T be made in a plant, only in a lab.

now I KNOW there's some reactions that can't be made in a laboratory, they have to be created in a plant, can anyone synthesize dna in a laboratory? no

just as at once point so much chemistry was unknown to us and know we can synthesize almost anything with a few chemistry lessons and the access to the right equipment and chemicals. I'm sure there's a secret to evolving plants to do just about anything we want, natural lsd, a tomato plant that grows 100 tomatos every plant, a new medicine discovered every year. a balance of chemicals whether they be medicinal, vitamin, protein, fiber or whatnot all in one plant that could give someone an extra 10 or 20 years of life. I'm just saying.

don't ask me why I become so fascinated with a concept such as 'natural lsd'

but if you took mescaline from a pill, wouldn't you think 'this feels like something that could come from a plant, it's so natural'

and it's out there, so who knows, who knows, maybe there's ALREADY a vine or fungus that produces it, finding out what it's use would be a big step to figuring out how to get an enzyme or whatever in a plant if you new it would help a plant in some way.

now that's just some lsd molecule, coming from someone who just wants to grow a plant in his backyard that had lsd already so he wouldn't have to buy it from someone.

imagine taking that concept, and applying it to taxol. yes, it HAS a function in a tree, because it GROWS in a tree, now find out WHY it's there, you could probably get the plant to want MORE of it if it helps it in a certain way.

here's something you don't see much, people try and find enzymes to activate chemicals in plants. But has anyone thought of, well, this plant produced so much whatever it is, to fend off infection, maybe instead of producing an enzyme, we genetically change that plant, to live in a condition where it's presented with so much infection that it genetically changes and produces 30 or 40 times as much of this chemical, right?

now as far as I know, that can't be done yet, you can't 'enhance' evolution, but what if it could be done, right? there's something for the future.

People could have fun experimenting with plants, get the plant to grow in ways that it produces different molecules. Who knows, you could get the hawaiian baby woodrose to grow in a way that it eventually produces lsd in order to help it's reproduction, or grow that tree that contains taxol in a way that it produces way more taxol, or different molecules more effective than taxol, or why not make the tree grow fast as hell. you could grow thousands of trees as small clones on 4 foot shelves in some big greenhouse/warehouse.

you could grow those trees containing taxol like you were growing weed! then you could extract and sell taxol til cancer was dying in your ass! you know?

well, alright, peace

 

[burnt]

I thought biosynthetic taxol production had been achieved already.

Yes it was achieved when the plant made it many hundreds of years ago. i think you mean production in cell culture and yes in some ways it has but still the goal is to make as much as possible in order for it to be economically more feasable.

anyway, that's true, now at this time these things aren't advanced. But in the future, who knows, maybe EVERY person with a science degree will be altering plants.

its quite common when studying plants these days to alter them genetically.

now I KNOW there's some reactions that can't be made in a laboratory, they have to be created in a plant, can anyone synthesize dna in a laboratory? no

yes you can. smaller fragments synthetically, big fragments just use the cellular machine.

but if you took mescaline from a pill, wouldn't you think 'this feels like something that could come from a plant, it's so natural'

DMT was first discovered synthetically. no one made the connection till about 20 or more years later.

imagine taking that concept, and applying it to taxol. yes, it HAS a function in a tree, because it GROWS in a tree, now find out WHY it's there, you could probably get the plant to want MORE of it if it helps it in a certain way.

yes you are right. it seems to be there for protective purposes because if you elicit the cell cultures with plant defense signaling compounds they produce more taxol, however it is limiting because taxol itself is toxic to dividing cells in general so one must design ways to continuously remove it from the culture as well as design genetic and environmental tricks to make the plant utilize much of its resources to making the compound you want. this stuff is being done but its not easy and more fundamentals about biosynthetic pathways as well as genetic regulation must become more clear for the science to progress further.

here's something you don't see much, people try and find enzymes to activate chemicals in plants. But has anyone thought of, well, this plant produced so much whatever it is, to fend off infection, maybe instead of producing an enzyme, we genetically change that plant, to live in a condition where it's presented with so much infection that it genetically changes and produces 30 or 40 times as much of this chemical, right?

you can trick plants to think they are infected and often they do produce more of certain chemicals and less of others. however what you are saying is purposely apply selection pressure by a pathogen until the plant evolves a stronger defense mechanism against that pathogen. why yes this is done all the time with conventional plant breeding. however getting a plant to produce 30 to 40 times more of a chemical is not always possible in a natural environment. because that plant needs to allocate resources to many other life functions. genetic and metabolic engineering will be required for certain kinds of compounds in the yields desired, because the plant will simply never want to make so much of certain compounds purely for fitness reasons either because they themselves are toxic or require many resources.

now as far as I know, that can't be done yet, you can't 'enhance' evolution, but what if it could be done, right? there's something for the future.

thats being done now. both through conventional breeding as well as genetic manipulation.

People could have fun experimenting with plants, get the plant to grow in ways that it produces different molecules. Who knows, you could get the hawaiian baby woodrose to grow in a way that it eventually produces lsd in order to help it's reproduction, or grow that tree that contains taxol in a way that it produces way more taxol, or different molecules more effective than taxol, or why not make the tree grow fast as hell. you could grow thousands of trees as small clones on 4 foot shelves in some big greenhouse/warehouse.

these kind of things are going on minus the lsd part. economics dictates where research goes often, supply and demand.

you could grow those trees containing taxol like you were growing weed! then you could extract and sell taxol til cancer was dying in your ass! you know?

this drug saves many peoples lives and to make it cheaper and more available people are working hard trying to figure out the kinds of things you are mentioning to make that possible.

 

[imachavel]

damn dude, are you a super genius or what? I don't understand how someone could know so much of this stuff, but then again I know NOTHING so maybe you're just a regular studied average scientist Joe.

well crap, then I guess all that's being done already.

I thought someone said you couldn't enhance evolution yet, that dna takes so many thousands or millions of years to make major changes without gene transcription.

well here's something, I hate to bring this up, because people think this natural lsd thing had gone TOO far.

has anyone thought of trying to manipulate a woodrose plant to produce as many ergotamine and lysergic acid products as it possibly could synthesize? it already produces what... a hundred different ergotamine and ls products, why not see if it could enzymatically create another hundred. See, I know nothing about this.

if I had the patience, I'd get a degree in plant genetics or some crap, and set up a lab, and try and grow different specimens of hundreds of different plant by, doing whatever you'd do to do that. But for what, drugs? I mean, I'm not going to get a 6 year degree and try and major financially in this business just to play albert hoffman in my basement. But a cool idea, huh!?



maybe I should start a new topic, medicinal plants, which ones help.

 

[deedle-doo]

I thought someone said you couldn't enhance evolution yet, that dna takes so many thousands or millions of years to make major changes without gene transcription.

Remember how evolution works. For evolution to occur in a system you must meet four conditions:

1. There is a struggle to survive so not all critters make it.
2. The strongest or best adapted survive and contribute to the next generation.
3. Traits are heritable.
4. There is an engine of random change in traits.

You can enhance the tempo and mode of evolution in a domestic population by manipulating any of these. To do these manipulations to a wild plant you must first domesticate it. You will be able to push a hardy generalist plant much further much faster. A weak or picky plant may take numerous human generations to get it right. We can back-door this process if we master plant developmental genetics.

DNA lesions are simple chemical reactions. Lots of nasty stuff can happen to DNA. The severity of the outcome is really dependent on where you break your DNA and how well the cell copes with the lesion. One pretty cool thing is that these lesions will not affect your offspring if they happen anywhere but your primary sex organs (testies and ovaries.)

 

[deedle-doo]

right now genetic engineering is very new, but who knows what microtechnology they can achieve, maybe one day synthesizing a proten will be like playing with a shaping device on a computer, entering the new molecule you want to experiment with, then adding it into the system, and letting some machine take a day to fold all the proteins to see if an enzyme is possible to create this molecule, coming back in the morning, and seeing 'what's in the microwave'

I love this idea and I beleive it will manifest in some way or another. Only the proteins will shape themselves, you will just input specifications. These proteins will then be plated in a monolayer with active sites up. Permanent catalytic disks housed in giant reactors producing the substances of the future.

I love the other future idea you had too. The one where people in general are educated enough about modern science to do this kind of thing in the home. I am much more pessimistic about this one though. As the science become more complex at an increasing rate the gap between what the cognoscenti and the layperson knows will grow unless modern science education gets a serious kick in the pants.

The science will get there but nobody will care much. People will be much more concerned with the advanced products produced by exploiting the science than understanding the intricacies.

 

[deedle-doo]

if I had the patience, I'd get a degree in plant genetics or some crap, and set up a lab, and try and grow different specimens of hundreds of different plant by, doing whatever you'd do to do that. But for what, drugs? I mean, I'm not going to get a 6 year degree and try and major financially in this business just to play albert hoffman in my basement. But a cool idea, huh!?

ha! Yeah I guess the idea would be to get filthy stinkin' rich by producing taxol or something and just do some plant genetics in the yard of your mansion in the islands.

 

[imachavel]

well, I'm glad you like the idea.

I wish psychedelics were still legal when this process became popular, who knows, maybe albert hoffman would have engineered some pretty cool plants.

by the way? how far HAVE people taken genetic evolutionary enhancement. I only know about cannabis.

plus, some genetics are easy to mutate, some aren't. How long would it take to get a plant that didn't produce flowers to produce flowers? how much stress and regrowth would THAT take.

I'm saying it'd be cool if they could somehow isolate dna, stress a part of it, and then regrow an entire plant and, like I was saying, see if you could get a tree that didn't produce flowers to produce flowers. high tech science, huh?

 

[burnt]

imachevel, i studied and worked on this stuff for a quite a number of years now. i could go on and on and on. im just trying to give you some information, however id recommend getting some books/take some courses on the subject or what not. knowledge is key.

but anyway.

by the way? how far HAVE people taken genetic evolutionary enhancement. I only know about cannabis.

very far. imagine what food crops were like before they were heavily domesticated. often barely edible at least to our modern tastes.

plus, some genetics are easy to mutate, some aren't. How long would it take to get a plant that didn't produce flowers to produce flowers? how much stress and regrowth would THAT take.

to get a plant that does not flower mutated enough to produce flowers would be tough. its a complicated interplay of many factors that induce flowering. sometimes its hard enough to get certain plants that normally make flowers in wild to make them in a greenhouse.

'm saying it'd be cool if they could somehow isolate dna, stress a part of it, and then regrow an entire plant and, like I was saying, see if you could get a tree that didn't produce flowers to produce flowers. high tech science, huh?

the shear number of mutations needed to cause a gain of function trait (especially one as complex as making flowers) would pale in comparision to the loss of function traits caused by such random mutation and hence kill or weaken most mutants. many trees do make flowers and the ones that don't don't need to to.

 

[deedle-doo]

imachevel, i studied and worked on this stuff for a quite a number of years now. i could go on and on and on. im just trying to give you some information, however id recommend getting some books/take some courses on the subject or what not. knowledge is key.

Word.
You'll have fun learning this stuff too. Knowing the basic mechanisms of how life works makes the whole world more stimulating. We tend to take the natural world for granted but if you scratch the surface you'll find it is beautiful all the way down.

Trees are awesome, humbling beautiful things. They are more spectacularly beautiful once you grok that they build themselves from invisible gases! And you can understand the mechanisms by which they build themselves in great detail if you want. After you have made all this knowlege part of you the next time you are 'augmented' in an old growth forest you'll have a completely different and, IMO, more meaningful experience.

Understanding these things is not hard. It should be no harder than teaching yourself how cars work or learning rosters of sports teams. We all have the gear, the trick is to give a shit.