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Suppose that there is a substance that is produced in nature by an organism. This substance is rather desirable. The reason this substance is desirable can be anything: Whether it is because it is a protein that can treat or cure a dreadful disease, because it enhances the abilities of a normal human (ie. the spice in Dune), or because it simply has some useful applications.

Now, it is known what organism produces the desirable substance and where said organism can be found. With that information, what is to stop a well-funded and well-equipped research program from sequencing the genome of the organism and splicing the genes responsible for production of the substance into a bacterium, and then proceeding to mass-produce the substance afterwards? What difficulties could a fictional research initiative have with producing a desirable substance through genetic engineering?

In real life, most Insulin for treatment of diabetes is produced from genetically engineered bacteria.

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    $\begingroup$ Welcome to the madhouse! Please check out the tour and help center so you can learn what kinds of queries we accept here and also how to compose good questions and answers. As of now your question is (deliberately?) overvague and broad in nature. You're basically asking for lists of substances & difficulties. WB.SE works on the principle of one single focused question get one single focused answer. Am going to vote to close your question while you edit it to conform of forum norms. Specifically, focus on a single issue or problem you are experiencing with building your fictional world. $\endgroup$ – elemtilas Jul 13 at 19:20
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    $\begingroup$ There is nothing "to stop a well-funded and well-equipped research program" from eventually developing a process for producing or (semi-)synthesizing the substance. However, you may be grossly underestimating the cost of the endeavour; in very many cases it makes much more sense to grow the organism in question and harvest the substance. For example, we are perfectly capable of synthesizing starch, but we don't -- we grow potatoes and grains; or consider ethyl alcohol: both synthetic and biological sources are used, depending on the business case. $\endgroup$ – AlexP Jul 13 at 19:25
  • $\begingroup$ @AlexP We still can't manufacture spider silk nor honey to my knowledge. $\endgroup$ – Lupus Jul 13 at 19:30
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    $\begingroup$ @Lupus: Honey is not a chemical substance; it is a solution of sugars in water with a few other components in much smaller amounts. Water is aplenty, and sugars we can make with ease. Funny you should mention spider silk... $\endgroup$ – AlexP Jul 14 at 2:12
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The organism that was discovered has evolved a foreign system of encoding genetic information. Normally, genetic information is encoded in DNA, but this organism encodes it through some other method. Therefore, genetic engineering becomes useless because there are no genes to sequence, splice, etc. The scientists will have to figure out how to translate the organisms encoding system into DNA before they can do any tampering.

As a side note, one possible cause of this evolution is that there was a virus that modified the organism's DNA in a way that was fatal to the creature. However, a couple organisms developed this separate form of encoding as a backup for critical parts of the cell/system/organism. When DNA tampering was detected, the cell would use the other encoding to keep the important parts running while the DNA was repaired. Over time, more and more of the DNA was encoded in this separate encoding system until the DNA became useless and began to disappear. By the time the organism is discovered only trace amounts of DNA segments remain.

EDIT:

To show how this answers your question:

What is to stop a well-funded and well-equipped research program from sequencing the genome of the organism and splicing the genes responsible for production of the substance into a bacterium, and then proceeding to mass-produce the substance afterwards? What difficulties could a fictional research initiative have with producing a desirable substance through genetic engineering?

There's nothing stopping the research program from capturing the organism and attempting to find DNA, but since there is little DNA to be found, they wouldn't be able to splice any effective DNA into a bacterium. Therefore, they cannot mass-produce the substance.

Even if they could determine the organism's encoding system and sequence it's 'genome', they would have to find a bacterium that uses the same encoding system so they can splice the genome in. They also would have to find enzymes to splice it in. Both of these would be hard to find. Basically, the research program would have to completely rediscover genetic engineering, but for the new encoding system. This would be an extremely difficult task, and may even be impossible if no other organism uses the same system.

The only other way to possibly discover how to mass produce the substance would be to figure out how to translate between DNA and the foreign encoding, so that they can create their own sequence of DNA based on the 'genome' they discover. However, this would also be extremely difficult because only one organism uses this system, so they can't find similarities or differences between different 'genomes'.

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    $\begingroup$ You can improve the quality of your answer, and thereby your score, by better tying your creative answer to the original question. Your answer is providing specific mechanics of a solution without specifically addressing points of interest raised by the original question $\endgroup$ – EDL Jul 13 at 22:32
  • $\begingroup$ @EDL Thanks. I've edited it to add a connection to the question. Is it what you were looking for? If not, I don't quite understand what it is that I'm missing. $\endgroup$ – dragonFire Jul 14 at 0:06
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Paclitaxel is a complicated molecule. And a good example. It is made in the bark of yew trees and is a really good chemotherapeutic.

paclitaxel https://en.wikipedia.org/wiki/Paclitaxel_total_synthesis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901146/

Biosynthesis of the anticancer drug Taxol in Taxus (yew) species involves 19 steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methyl erythritol phosphate pathway for isoprenoid precursor supply. Following the committed cyclization to the taxane skeleton, eight cytochrome P450-mediated oxygenations, three CoA-dependent acyl/aroyl transfers, an oxidation at C9, and oxetane (D-ring) formation yield the intermediate baccatin III, to which the functionally important C13-side chain is appended in five additional steps.

Yeah, what he said.

Or imagine this. DNA codes for proteins. You can make the proteins. Imagine proteins are craftsman, each one working with the product. You can hire them. But you need to make sure that each one has the materials he or she needs, and that the product is passed to each one in the right order under the right circumstances. It is tremendously complex biochemistry. The DNA coding for the proteins carrying it out is only the first step - and how do you even figure out what the proteins are that carry it out?

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This is actually a plot point in the rather excellent series Troy Rising because there's an alien species addicted to maple syrup. So, to answer your question, let's take a look at what you're asking:

Now, it is known what organism produces the desirable substance and where said organism can be found. With that information, what is to stop a well-funded and well-equipped research program from sequencing the genome of the organism and splicing the genes responsible for production of the substance into a bacterium, and then proceeding to mass-produce the substance afterwards? What difficulties could a fictional research initiative have with producing a desirable substance through genetic engineering?

You have the 'xenobiology' tag, so there's a really quick fix there - the biology just doesn't add up. It's an R-enatiomer, it uses elements not found in Earth biology, or perhaps it doesn't use double-helix DNA. But let's go a step further and figure out why you can't synthesize these products using the xenobiology's equivalent of bacteria (or, in the case of Troy Rising why they can't just engineer Earth bacteria to produce maple syrup.)

And the answer is complexity. You said 'substance', which includes mixtures. Synthesizing something like insulin isn't complex at all for a cell to do, because it's a merely a single protein. Cells make proteins all the times, so all that's needed is a specific order and you're good to go. The cell is already equipped for it. Maple syrup, on the flip side, is mostly sugar - but it also contains complex substances, like phenol structures and hormones, which is transformed to even more complex forms during the boiling process from sap to syrup.

The chemical cocktail in your question can have hundreds of reasons why just splicing the DNA in won't work - because a single bacteria just isn't complex enough to make all the components of your compound mix them together in just the right way. You'd need a series of specialized separate cells, each producing separate products and a system to mix them all together - basically, the host organism.

If you don't like that, there's another answer too - the RNA of bacteria is prone to mutation, certain sequences especially, and bacteria which produce the compound will have too large of a percent of tainted product to be helpful.

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    $\begingroup$ I can give you a great example. WOOD no matter how much spicing you do bacteria are not going to produce wood because it is complex containing many materials and has to be shaped by the cells in a specific way to get its desirable properties. $\endgroup$ – John Jul 14 at 14:03
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what is to stop a well-funded and well-equipped research program from sequencing the genome of the organism and splicing the genes responsible for production of the substance into a bacterium, and then proceeding to mass-produce the substance afterwards?

The world is full of useful compounds that we can't synthesise in this way. DNA is not a magic wand that can be waved and have it make everything you could possibly want, for a number of reasons.

Willk gave the example of paclitaxel... this is easily synthesised by yew trees using metabolic pathways they use for other useful purposes, but those pathways are very different to the ones found in bacteria and yeasts so you can't just splice in a few bases and hope for the best. The compound is also quite toxic, which may also make it hard to synethesise. Transgenic biosynthesis of the chemical is now possible, but it took a long time and a fair amount of money to make possible.

Lupus mentioned spider silk in the comments above... they're correct that we can't synthesise actual strands of silk, but we can synthesise the building blocks of silk (I seem to recall this has been done using genetically modified goats who secreted useful compounds from their mammary glands; it isn't just bacteria that can be engineered to help here!). Correctly assembling those building blocks and then processing them in the correct way to get something with the right physical properties at the end is a much harder proposition.

Some compounds aren't encoded in DNA at all. Non-ribosomal peptides cannot be synthesised directly by DNA because they use structures or amino acids that DNA cannot encoded. Instead, the usual protein synthesis pathways are used to assmeble suitable synethetase enzymes which then do the hard work. Determining how a non-ribosomal peptide is assembled may be a non-trivial task, and until you do you cannot synthesise the compound without the source organism.

Sometimes the DNA of the organism itself isn't enough. Many bacteriophages have a payload that encodes for chemicals that infected bacteria will then produce. If infection rates are low, cultures of your source bacteria may not include infected bacteria and so won't produce the compound you want, and this issue may not be trivial to diagnose and fix.

In real life, most Insulin for treatment of diabetes is produced from genetically engineered bacteria.

Lets have a look at a different class of drug... monoclonal antibodies. Antibodies are interesting because your DNA does not encode for them directly... instead a basic repertoire of assembly techniques is encoded and then your immune cells use a bunch of tricks to generate a colossal variety of possible antibodies. Some will be more effective than others, and highly effective antibodies are valuable drugs, but as they are not encoded in DNA you can't simply splice an antibody-fabricating DNA segment into a yeast and get useful pharmaceuticals out.

The technique for making monoclonal antibodies is now relatively well established and used for a number of treatments. It doesn't use bacteria, but it does use some clever bioengineering.

Very loosely speaking, you need to:

  1. Get a antigen to trigger an immune response in a target animal, like a mouse or bunny
  2. Harvest B-Cells that produce an antibody that binds to the antigen
  3. Fuse those immune cells to a B-cell cancer such as a myeloma.
  4. Culture the fused hybridoma cells, being careful not to include unfused myeloma cells.
  5. Separate out and culture your hybridoma cells, and wait for them to start oozing the antibody you need.
  6. Collect some of the juice, test it against the target, keep the hybridoma lines that produce the best juice.
  7. Profit! Possibly. Depending on how expensive the last 6 steps were, and whether they succeeded.

If it were possible to do this without giving small fluffy animals cancer and maintaining cancer cell lines, without the hassle of fusing cells and culturing hybridomas, they you can bet it would be done because monoclonal antibodies are super effective for all sorts of things.

We can't, yet, because biosynthesis is hard. So now you know.

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