Build Your Own Virus 381
Wire Tap writes "Scientists have assembled the first synthetic virus. The US researchers built the infectious agent from scratch using the genome sequence for polio. The most amusing part is this snippit: 'To construct the virus, the researchers say they followed a recipe they downloaded from the internet and used gene sequences from a mail-order supplier.' Heck, don't we all have our own mail-order suppliers for gene sequences?"
Re:Huge medicine possibility (Score:5, Informative)
So if the virus mutates (which isn't likely, given that most mutations happen during genomic replication) it would just sit there, doing nothing. I suppose that potentially another, wild-type virus could coinfect the cell with the mutant (also relatively unlikely) and supplement the necessary machinery, but this is no more likely than if the wild type virus itself had mutated, in which case you have a new strain on your hands (although with the originally synthetic mutant, it would still need to be supplemented by the wild type each time it infected a cell in order to replicate).
While you do raise a good point about mutation, it's not any different than what happens in nature. In fact, it's probably far more controllable.
Re:ebola ain't no joking matter (Score:5, Informative)
But it's also limited. Why is it that we haven't had a major outbreak all over the world, killing billions? Ebola is an RNA virus, which makes it very unstable (RNA is far less stable than DNA, and more prone to mutations). Because of this, Ebola was able to evolve in the first place in to something so deadly, due to its high mutation rate.
But Ebola never lasts too long, it comes in outbreaks, then it goes. That's because of two reasons. One is that the same instability which made it deadly also causes it to become ineffective at a quick pace. Mutations can work against these organisms too. The other reason is that it kills too quickly. It can't spread because people die before it gets a chance to move effectively. It's just too damn lethal.
Ebola is terrifying, but it's not all powerful. Any kind of pathogen has to balance infectivity with lethality, and Ebola is too far on the lethal side to be massively infective right now, thankfully.
Re:Huge medicine possibility (Score:1, Informative)
http://www.evergreen.edu/phage/phagetherapy/pha
More details at Science and Nature (Score:4, Informative)
Cello, J., Paul, A.V. & Wimmer, E. Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science published online, doi:10.1126/science.1072266 (2002).
Re:Wasn't AIDS the first? (Score:1, Informative)
Re:Worrisome? (Score:3, Informative)
Still, by biotech standards, this is the equivalent of doing science in the garage. At least the smallpox genome is ~25x bigger than polio.
Re:Methods not suprising (Score:4, Informative)
In fact, it's now gotten to the point that it's way more economical for small and medium sized labs to order out, rather than doing their own synthesis
Statistics, Nature, and Suicide Genes (Score:5, Informative)
And you know what? This has already happened. That's how viruses can replicate inside us now. They have some of the same genes, stolen from host cells long long ago.
So, you have to ask yourself this: How is what I'm doing any different than what nature itself is doing? It's not really, and in fact, it's far more controllable and less likely to happen than in nature itself. In nature, the virus has less hurdles to go through to create this sort of doomsday scenario you're thinking of. With us, it's got to go through a lot more trouble. It's not impossible, but it's really really unlikely.
You also have to realize what I mean by "suicide gene". It's not something that will randomly kill whatever cell it's expressed in. We, and many many others, are using a standard gene taken from herpes called Thymidine Kinase (Tk). Humans have a version of this gene too, but it's far more picky than the herpes one. Basically, if you use the herpes gene, you can treat with a prodrug like gancyclovir, which normal human Tk will ignore, but herpes Tk will incorporate in to DNA. This will cause the DNA to be unable to replicate, and the cell will die. Note that this can't happen without administering the drug. The provides yet another major hurdle for the virus to overcome in order to attain its "deadly capability".
Stop being so scared of what humans are creating. Nature is doing a far better job of finding ways to kill you and the rest of humanity than I or any other molecular biologist could ever hope to devise.
Re:A typo, surely? (Score:2, Informative)
You send off to a mail order place asking for a DNA sequence AGTTGTTGTTACGTT (or whatever), and they send you back 2uL of it in solution.
This has been pretty standard ever since I did my genetics honours work (1993).
There's A Reason Why Genes Are Conserved (Score:3, Informative)
My understanding of the poliovirus is that it's protein capsule is very highly conserved. The gene for its pieces is actually one polyprotein which is cleaved after the pieces interact. The pieces of the each subunit have to fit together perfectly, and altering the genetic structure of the gene can destroy those interactions, making it impossible for the virus to assemble correctly.
So the antibodies will probably be just fine. Besides, the Salk vaccine is heat-killed virus anyways, so you could probably apply the same treatment to your mutated virus, and have an effective vaccine. Or, since you know the makeup of your synthesized original, you could mess around with its genetic structure and create a live attenuated vaccine (another type which exists for polio, and can be more effective).
Notes from an Ex-molecular biologist (Score:2, Informative)
This news should not be surprising. The technology to synthesize multiple large genes has been around for years; and it has been known that the pieces could be combined in a host cell to yield whole, infectious virions. The novel thing here is that somebody has combined the two technologies, creating the polio genes synthetically before putting them into a host.
Two older articles describing the combination of cloned viral genes in vivo to make infectious virus are:
This article [nih.gov] showed that the bovine herpesvirus genome could be cloned into a bacterial vector, maintained indefinitely, then reintroduced into cow cells to produce active virions.
This article [nih.gov] showed that infectious rabies virus could be produced by putting cloned rabies genes into a suitable host.
Nowdays, if you have a gene sequence, you can synthesize it in pieces and assemble it (with modifications, if you choose) with PCR quite easily. You don't need any source material from the original organism. I synthesized a small gene from scratch myself, once, back when I was an underpaid M.S. in a biotech company.
Of course, I never tried this with a whole FREAKIN' POLIO VIRUS!!!!! WTF!!!! Didn't these guys ever read "The Stand"?!
-dexter ("Don't Fear the Reaper", my ass) riley
Re:Huge medicine possibility (Score:2, Informative)
Gene search ones, ones with GFP, ones with the tet transactivator, etc etc.
They work great, infect all types of human and mouse cells with great efficiency. They are all what is called SIN vectors : "Self INactivating". Their LTRs (control centers) lack promoters and enhancers, they lack Psi packaging signals for the viral RNA to be packaged, and (once integrated into the cell's genome) lack all lentiviral/retroviral structural genes (gag, pol, env, rev, tat, etcetera) which make a virus a virus. Safety with regard to virus gene therapy has been extensively studied in the past 10 yrs - just check out PubMed.
If in the event that this vector infects a cell already infected by a real pathogenic lentivirus (ie HIV-1)where the structural genes already are (in trans) it STILL wouldn't generate further vector virions because the viral vector provirus lacks LTRs to transcribe the viral RNA, and even if it somehow was transcribed it couldn't be packed into the protein particle as it lacks the RNA secondary structure element known as the psi signal. So no "new hybrid cell/virus that carries the deadly portion and the reproduction capability". No way of that happening that I can think of.
Onyx Pharmaceuticals (I think) has had inital success with this approach- using a virus (Adeno?) which specifically infects cells lacking p53 (many tumor cells) and had promising results with head and neck tumors (here's a ref:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
Finally a subject on