SF writer trying to get facts straight

[Mokele]

But wouldn't an RNAase be useless against a virus that's sealed safely inside it's capsid?

[Mr Skeptic]

Yes, but a virus that is sealed safely inside its envelope and/or caspid also isn't attacking you (yet). The RNA must leave the caspid before it can attack you, then it may be vulnerable to RNases.

[Mokele]

Doesn't it leave the capsid inside the cell? Are these RNAses intracellular or extracellular?

[Mr Skeptic]

The RNases are intracellular AFAIK (maybe some in the digestive juices too?). There shouldn't be RNA floating around extracellularly anyways. With no ribosomes, what would it do out there?

[CharonY]

Actually there are extracellular RNAs. They are not involved in translation, but in a number of other processes, including as cofactors.

[writerchick]

I can't tell you how wonderful y'all's help has been! I've been reading like mad, but a lot of what I read is so general and I'm not able to extrapolate the specific details to answer my own questions, so thank you, thank you!

 

So it is conceivable that your subspecies (or uberspecies) could have an enzyme that hydrolyzed (cut) part of the grip virus capsid, and thereby prevented it from binding to cells. Of course, as soon as this fact was recognized, that enzyme would become the cure: pharmaceutical companies would simply manufacture the enzyme, for intravenous injection. Instant cure.

 

What I've come up with so far, for the book, is that the virus is transmitted via insect, maybe mosquito, and attacks humans. It's deadly with no known cure. The human population dwindles. The subspecies is created such that their bodies don't manufacture the protein targeted by the virus. The cure is an enzyme in the subspecies's saliva, making the subspecies very valuable to infected humans.

 

But now I need the enzyme to not be manufacturable (otherwise, subspecies loses its value). Any ideas why this would be so? Manufactured enzymes would be chemically identical to the naturally-occurring one, right?

[Mr Skeptic]

Note that if the subspecies does not manufacture the protein targeted by the virus, it would not need anything else to provide immunity. So it would just be a coincidence if the subspecies had an enzyme in their saliva that would be a cure. I'm guessing you want this as part of the plot though.

 

I'm not too familiar with the process of producing enzymes to order, but I think it goes something like this. First, they have to isolate the protein in the saliva responsible. Second, they have to isolate the gene responsible for the protein, not all that hard but rather time-consuming (or they could read the protein and design a gene to produce that sequence). If you want to make this more difficult, the protein may naturally fold into a useless shape and need chaperonins so that it folds into the proper shape. Finally, a genetically engineered microbe could be made to make this enzyme, either by retrovirus or plasmid (if there are other methods I don't know them). Finally, production can start. I have no idea how long this all would take, but if you had a rapid plague, it could be that this would take so long that the plague would run its course by the time a cure could be manufactured.

[GDG]

A few ideas:

• Having an insect vector means that the main focus for controlling the plague will be vector control, i.e., spraying the mosquitoes, wearing protective garments, etc. Also, likely that this will be a much bigger problem in the developing nations than in the developed world -- cf. malaria, etc. Your best and fastest epidemics are usually spread directly, human to human.
  
• Are you sure you want the cure present in spit? You might be able to get more drama out of the situation if the cure is in their blood:
  
  Frank_sub slowly retreated from the mob, until he reached the wall and could go no further. Arthur, in front, coughed wetly into his sleeve, and wiped the blood away on the back of his hand. "Now, Frank_sub, we don't wanna hurt ya. We just need ya to spit inta this cup here."
  

  
  OR
  

  "Frank_sub slowly retreated from the mob, until he reached the wall and could go no further. Arthur, in front, coughed wetly into his sleeve, and wiped the blood away on the back of his hand. "Now, Frank_sub, we don't wanna hurt ya.
  We just need a little bit o' your blood
  ..."

  
  

• If the Subs have been engineered to express the cure protein, then it will also be no problem to manufacture the protein. It is possible to culture human cells, and collect the protein. Could be expensive, but not impossible.
  
• If the Subs express the protein, you'll also have to think of a reason why gene therapy won't work on the normals. This would be a natural solution, if it would work, and there would be great incentive to make it work...
  

 

Short proteins (oligopeptides) can be made chemically. Longer proteins are usually expressed recombinantly in a host cell. When a mammalian protein is expressed naturally, it is often subject to post-translational modification. This can be adding carbohydrate (sugar) molecules to certain parts of the protein (a process called "glycosylation"), or lipids or other molecules, cross-linking parts of the protein (typically by disulfide bonds), cleaving parts of the protein, etc. The way that the linear polypeptide chain folds up to make a functional protein can be critical. If the protein doesn't fold right, it is "denatured" or misfolded, and won't have the correct activity (it may have no activity at all).

 

When proteins are expressed recombinantly (i.e., in a host other than the original source of the protein/gene), you can encounter problems. If you express a mammalian protein in bacteria (E. coli is a favorite host), no glycosylation occurs. For some proteins, this is not a problem (and some proteins just are not glycosylated to begin with), but for others, it can affect how long the protein lasts in the body, and in some cases glycosylation is essential for activity of the protein. If you express the protein in yeast, you'll get glycosylation, but it will usually be somewhat different from the native glycosylation pattern (yeast may use different types of sugar, and may add more or less sugar than the native form). Expression in mammalian cells is the most difficult and expensive, but is definitely doable on a commercial scale.

 

I can't think of a scientific reason why it would be impossible to manufacture the cure protein if the Subs can express it naturally. Even if you postulated that the Subs have a new and different glycosylation pathway (which would require a huge effort, because nearly every protein in the body would require some redesign), manufacturers would simply use cell cultures of Sub cells for manufacturing. Even if the cure protein is previously unknown, it is only going to be an obstacle for a matter of weeks or months (much less time than it would take to design and raise the Subs).

 

Suppose the Subs were created for a different purpose, and just happened to be immune to the Grip. And suppose that it was later discovered that a protein in Sub saliva functioned as a cure. Presumably, researchers would know how the Subs were changed genetically, and one of those changes would be responsible for the cure. Not too many things to check.

 

Even if all of the records had been lost or suppressed, Researchers would collect saliva samples, and examine the proteins contained in the samples by gel electrophoresis (this is a lab technique that separates proteins based on their electrical charge and size). If there were only one or two proteins in Sub saliva not found in "normal human" saliva, that would be your dead giveaway. Scientists would extract and purify more of that protein, and test it against the pathogen. It is not too difficult to sequence part of the protein, and the probe the genome or a cDNA library for the likely gene that encodes the protein. Even if the cure protein was only an altered form of an existing protein, there are not too many proteins in saliva: researchers would simply test each fraction for activity against the pathogen until they identified the responsible protein.

 

Likely to take a matter of a few weeks to identify the protein, and several months to start manufacturing commercial-size quantities. However, the biotech/pharmaceutical industry as a whole probably does not have the capacity to make enough of any kind of protein to treat the global population, if the disease is pandemic. Perhaps that is your solution: the protein can be manufactured, but not quickly enough to get it to everyone. Or perhaps manufacture is controlled or suppressed or sabotaged by some group of evil-doers.

[writerchick]

Thank you, Grant!! That is very helpful information!

[GDG]

Happy to help. Have my own SF novel simmering on the back burner...

 

BTW, the CDC has a free monthly publication called Emerging Infectious Disease that you might find helpful.

Edited March 3, 2009 by GDG
adding link

[writerchick]

Ooh thanks! I had some concerns about using mosquitos because we could spray for them, but that CDC periodical had an article about a parasitic mite causing skin lesions in humans...

 

Good luck with your writing! Writing fiction is even more fun than reading it.

[throng]

In the stuff I read by Barbera Knowles, who as far as I know is quite credible, the study of junk DNA in rats was shown to transpose (Junk is a transposable element) during the emryonic stages then serve no genetic function after birth, and she basically says that it seem junk DNA is actually a necessary transposable element for embryonic developement and is in fact not junk.

 

Still, it is also apparent that parts of our DNA is not human in origin, which is the case for respective species of animal too.

 

And viruses do attach their DNA strands to ours and we can pass them on, so viruses might be a vital factor in evolution of species, I wildly speculate.

[Lessian]

This is all sounding way cool. I am not even a writer and my mind is buzzing with possibilities lol.

writerchick, if ever you need someone to proof read your script or offer comments, feel free to buzz me. Its so hard to find good science fiction nowadays, would love it if yours joins the ranks

[writerchick]

Hi everyone,

 

I wanted to return here to thank you all very much for your help! At long last, I'm almost ready to release this novel! It's scheduled to be out Dec 1. I'd like to offer those of you who've helped me a free e-book copy as my thank you -- and hope I don't make you cringe with the wrongness of the science! Drop me an email here or through my web site to tell me what file format you prefer (epub, mobi, PDF) and where to send it.

 

Thanks again for your awesome guidance!