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Science

Build Your Own Virus 381

Posted by michael from the just-like-sea-monkeys dept.
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?"
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Build Your Own Virus

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  • I remember my BioChem classes (10+ years ago), and it seemed even back then that to some degree the technology was already there. It does make you wonder if this is truly the first one, or just the first one to be formally announced.
  • What if, say, a virus could be designed to destroy cancer cells? What if a virus could be designed to infect parasites? If the drug companies start doing this, it's only a matter of time before they can make viruses that can target disease cells extraordinarily effectively.

    • True, just like there were a couple computer viruses that searched out and destroyed the bad ones.

      of course, this wouldn't work. viruses can't attack each other.

      perhaps we can make viruses to attack bacteria strains? but this is too questionable. what if you make a strain that kills off good bacteria that we need? no, too risky. kinda like the bacteria that eat petroleum, and could make it into some underground reservoir. just too dangerous

      so what good could these virii do for us? safely, not much. there's too many things that go wrong with simple chemicals we use in regular drugs, much less a biochemical virus, which is much more complicated than anything we can wholley, fully, and correctly predict

      • There have actually been studies on animals and even humans using genetically engineered viruses (not made from scratch) to do this kind of thing for years. They keep killing people though, so I don't know that they're having as much success as they'd like.
        • Early blood transfusions would kill people, as well. Seems like most medical technologies kill people in the early stages. The researchers just need to get it right. (Early blood transfusions killed people due to cross-species transfusions, and lack of knowledge of blood types.)

          Of course, this will open up a whole can of worms, too, I'm sure. Renegade viruses that we can't stop, etc.

          Sometimes I just have to wonder which innovation of humanity will kill us all off. =]

          -Sara
        • *THUDDUD*

          Oooh, verdamnt, not once more! Back to ze dravink board es ist. Igor, clear out ze body and vasche ze beakerz! Schnell! Ich must vork on the formula some more! Hunh...
        • Do you have a reference for this? I've never heard of using these sorts of things on people and killing them.

          There was one case out (in Pennsylvania, I think) where the doctor administered way way way too much virus, and the kid was already immunocompromised, and he basically died of toxic shock. Since then, I don't think anyone's done any real viral gene therapy on humans.

          But if you have references for this (particularly abstracts from medical journals linked from PubMed) I'd really like to see them.

          Oh, and as for killing animals with engineered viruses, I have personally seen plenty of animals that were not affected by engineered viruses that are administered. We generally have a pretty good idea as to what we've made before we go putting it in a living creature.
      • Viruses have already been employed in gene therapy, and actually this technique was involved in the first gene-therapy death. So, already been done and already wreaked unforseen havoc on at least one occasion, but the idea is that the virus alters the genes in a person's cells in a beneficial manner rather than in a way that causes the cells to churn out more viruses.
    • What if, say, a virus could be designed to destroy cancer cells?

      Until they mutate and we have that same viruses destroying healthy tissue. Besides, what would the immune response be? Would that make you sick?

      • Re:Huge medicine possibility (Score:5, Informative)

        by krmt ( 91422 ) <therefrmhere@yah o o . com> on Thursday July 11, 2002 @09:40PM (#3868391) Homepage
        This is a possiblity, but pretty much anyone who's serious about this (ie, actually doing work in the field) is using a virus that can't replicate on its own. It just doesn't have the machinery to do so, because we've taken it out all together. Believe it or not, the space in a viral genome is very valuable, and you want to make as much use of it as you can, so you take out everything that's not necessary to your work.

        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.
        • using a virus that can't replicate on its own. It just doesn't have the machinery to do so
          Uh huh. And just how many times has something that "can't happen" happend in research?

          You are putting a virus with no capability to reproduce in to a cancer cell with an over-ability to reproduce. Are you telling me there is abosoutly no way that a cancer cell will mutate, accept the introdouced virus and create a new hybrid cell/virus that carries the deadly portion and the reproduction capability? I don't ask if it's unlikely, but guaranteed impossible.

          I'd think this is especially bothersom with a virus that is as higly mutative as HIV is.

          • Statistics, Nature, and Suicide Genes (Score:5, Informative)

            by krmt ( 91422 ) <therefrmhere@yah o o . com> on Thursday July 11, 2002 @11:25PM (#3868757) Homepage
            Are you telling me there is abosoutly no way that a cancer cell will mutate, accept the introdouced virus and create a new hybrid cell/virus that carries the deadly portion and the reproduction capability?
            Nothing is guaranteed in life, especially the science of life. And yes, it is a possibility, but it's far far far less likely than creating a hybrid from a normal, wild type virus. The wild type virus already has the machinery to replicate, and thus is more likely to take the necessary cellular machinery with it.

            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.
            • (* 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. *)

              My understanding is that most viruses have evolved not to kill their host, otherwise they would shorten the time they can spread themselves around.

              HIV is one of the rarer viruses that *does kill* its host fairly easily.

              If the killer side is mixed in with the easy-to-spread features of say the common cold, then a killer cold could be put on the loose by some Osama-like madman (or madwomen. EOI=Equal Opportunity Insanity).

            • "I may not have morals, but I have standards."
              I always thought your sig was cool, until I learned that you are A MOLECULAR BIOLOGIST WHO GRAFTS SUICIDE GENES INTO VIRUSES TO PLACE INTO HUMAN BODIES!!!!!
          • I make recombinant lentiviruses every week in the lab. Probably made around 20 different ones so far.
            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? cmd=Retrieve&db=PubMed&list_uids=11892945&dopt=Abs tract)

            Finally a subject on /. that I know something about!
        • What happens if you cross a chicken virus with a human virus?
          You get the next plague.
          Those that understand my comments will remember the China scare from 2 years ago. Those that don't will think this is offtopic.
          Just because the virus doesn't reproduce doesn't mean it can't transfer it's genetic payload to something that does.
          • This is very true (you're thinking of influenza by the way) but the thing about the chicken strain is that it was able to reproduce in areas other than the upper respiratory tract, where the human influenza virus is stuck in. Mixing the human genes with the chicken ones allowed the new strain to reproduce in any human cell, which would have killed scores of people.

            This is a very real danger, but how does this change anything related to the technology? With the old technology, you could have easily done this by hand, rather than synthesizing from scratch, you could shuffle a bunch of coinfected influenza viruses around until you got what you wanted, essentially speeding up the natural process. You could also modify the existing virus to do this.

            Just like nature did in creating the Influenza strain you're talking about.

    • Re:Huge medicine possibility (Score:5, Interesting)

      by krmt ( 91422 ) <therefrmhere@yah o o . com> on Thursday July 11, 2002 @09:33PM (#3868359) Homepage
      What if, say, a virus could be designed to destroy cancer cells?
      Heh. This is exactly what my lab is doing, as are many others. We're using a modified adenovirus to deliver a suicide gene to cancer cells, thereby killing them. Not a new idea anymore at all (people have been working on gene therapy for over a decade) but it's one that takes a lot of time to put in motion. Just do a search on "gene therapy" and "viral vector" at PubMed [nih.gov] and you'll get more info than you ever wanted to know about what's going on.

      • Re:Huge medicine possibility (Score:5, Funny)

        by nick357 ( 108909 ) on Thursday July 11, 2002 @09:44PM (#3868405)
        "I may not have morals, but I have standards."

        When someone who is in the business of "using a modified adenovirus to deliver a suicide gene", is using a sig like this, it scares the bejeebers out of me...
      • (* We're using a modified adenovirus to deliver a suicide gene to cancer cells, thereby killing them. *)

        How does it tell the difference between good cells and bad cells? I read that cancer cells may differ by one or two genes from good ones. That is rarely enuf for a virus to lock onto, isn't it?

        Or, does it target a *kind* of cell, like a liver cell? In that case, couldn't you kiss the real liver goodbye?
    • As other posters have pointed out, the virus to infect cancer cells is too risky; in order to work, such a virus would have to be engineered to sidestep the body's own defenses. At that rate, there is too much risk it might go "wild" and start attacking other cells.

      Virii that attack bacteria (which are more typically called Phage) exist extensively in nature. They are one of the classic tools of molecular biology, well studied and characterised. Some strains are also nearly 100% lethal as they exist in nature. We are unlikely to improve on the lethality of phage with direct meddling - that is to say, by rewriting individual nucleotides one at a time (why below). In any case, in order to get all of the bacteria in your body with phage, your body would have to be inundanted with the phage. The phage don't hurt you, but you're body doesn't know that! The phage would send you into a state called Septic Shock, as you're own immune system's panic response killed you. We might engineer phage that don't set off our alarms - this has other risks, and this custom virus technology doesn't really help do this (yet.)

      I'm trying to include a minimum of background, so here I go - genes/DNA (a code of 4 monomers) code for proteins (composed of 20 monomers, the code is somewhat degenerate.) The sequence of these monomers determine the shape of the protein - some of these monomers contain polar (vinegar-like) groups which want to be on the outside of the protein, touching water, some of them contain oily (like olive oil in salad dressing) groups which want to be on the inside, touching eachother. Other, more complex factors also come into play, making the relationship between sequence and three dimensional structure (which determines function) highly opaque. The ability to predict how a 13 monomer long protein is shaped, and thus what it will do, is beyond our present capability.

      You could make up a sequence up the top of your head, but you'd have no way of knowing what it would actually do!

      This means that when you genetically engineer an organism you don't even want (generally) to type genetic changes into a keyboard. You want to import large, complicated pieces of DNA from another organism, and clone (move) the DNA into the organism you're tinkering with.

      There are situations where DNA you want is not available - for example, if I wanted DNA from the Ebola virus, I could not get it. There are other situations where you want to make single point changes in DNA, in order to see what happens (if, for example, you want to know if the single peptide you changed is important in the function of the protein.) However, this technology won't (if I understand it correctly) let you do that - their duplication of the virus genome was EXACTLY precise enough to get live virus; any errors in their DNA sequence that didn't render the virus nonviable wouldn't be caught.

      The upshot? This isn't a tremendous advance in our ability to customise organisms. With refinements, it might be, but right now all you would use it for is to get DNA that you don't have physical access too.

  • Finally! (Score:5, Funny)

    by Joe Tie. ( 567096 ) on Thursday July 11, 2002 @09:06PM (#3868225)
    From the article: injected it into mice to demonstrate that it was active. The animals were paralysed and then died.

    After decades of research, advances in biotechnology finally creates the long fabled "better mousetrap".

    • Re:Finally! (Score:3, Funny)

      by Kredal ( 566494 )
      Polio didn't kill the mice... the scientists were just careless and injected the saline solution into the mice's spinal cords, causing paralysation, and then death.

      False alarm, nothing to see here...

  • Worrisome? (Score:5, Insightful)

    by maynard-lag ( 235813 ) on Thursday July 11, 2002 @09:08PM (#3868231)
    Ok, wtf, from the article we have these snippets:

    Responding to criticisms that such research could lead to bioterrorists engineering new lethal viruses, the scientists behind the experiment said that only a few people had the knowledge to make it happen.

    and then the rest of the article is filled with stuff like this?!

    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.

    According to researcher Jeronimo Cello, the polio virus assembled in the laboratory is one of the simplest known viruses. "It was very easy to do," he said.

    "We've known this could be done. We've known it was just a matter of time before it was done," he said.

    Why shouldn't we be worried?

    • Re:Worrisome? (Score:2, Insightful)

      by billstr78 ( 535271 )
      I also hope that this sort of synthesized virus does not become another "Africanized Bee".

    • Re:Worrisome? (Score:3, Insightful)

      by Troodon ( 213660 )

      The reporting of this advance seems to be spun in two different directions by those reporting it:

      The dangers of the net, open reseach genetic databases: a modern terrorist's cookbook.

      A scientific advance, potential medical breakthrough with the posibility for radical vaccine developement etc.

      Perhaps its from different viewpoints within the institution/research group responsible. Id suggest going to the horses mouth should you have realplayer and listen to an interview by one of the researchers by the BBC radio4 program Leading Edge (Real Audio unfortunately) [bbc.co.uk]

    • Re:Worrisome? (Score:3, Informative)

      by nucal ( 561664 )
      According to Science [sciencemag.org] it took the group two years to synthesize the virus and the synthetic virus is 1000 - 10,000 times weaker than "natural" Polio virus.

      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:Worrisome? (Score:3, Insightful)

        by Rutulian ( 171771 )
        Still, by biotech standards, this is the equivalent of doing science in the garage. At least the smallpox genome is ~25x bigger than polio.

        Except that it still costs tens of thousands of dollars to run a lab capable of doing this. This isn't mix-and-match with chemicals from the local drugstore. It costs a lot of money to buy vectors, kits, reagents, perform sequencing, etc....

        It is kind of funny to find comments like this on a site like slashdot. People will post a comment jumping all over congress for creating the DMCA (i.e: "Just because software CAN be used for illegal activities doesn't mean it should be illegal itself because it has a legitimate use."), and then they will say things like: "This is dangerous research because it can be used by terrorists to make biogents!" Sheesh.

        • The point is surely that terrorists have cash. That's not the problem, it was always the know-how. I'm all for freeing knowledge, and using the Internet to brighten the corners of ignorance without forcing people to pay large amounts of money to go to Universities, but I like ice creams and walks on the beach. I don't like bleeding to death through my eyeballs so much.

          I have a degree in genetics, and personally wouldn't withhold knowledge from anybody. This is the kind of shit people like Monsanto and Celera would jump on in order to privatise data that should be publicly available, so we should proceed with care. but don't underestimate what's capable with biological weaponry, ever, ever, ever.

          *Washes hands after typing the words 'monsanto' and 'celera' twice in the same coment.*

    • We should be worried. we should be worried about a lot more than the creation of synthetic viruses. Take the Ebola virus [wisc.edu] - 90% fatal, compared to the smallpox fatality rate of 30%. We know a lot about the genetic structure of Ebola [wisc.edu] and the details of its genome are at a universtiy library near you; see Sanchez, A., et al. (1993), "Sequence analysis of the Ebola virus genome: organization, genetic elements and comparison with the enome of Marburg virus", Virus Research 29, 215-240(1993).

      But nobody is going to go to the trouble of synthesyzing an Ebola virus because it's too much trouble and there's a better way to turn it into a Weapon of Mass Destruction (WMD). Ebola has just seven genes and only one of these produces the substance that causes the 90% fatality rate - Ebola glycoprotein. The gene for this protein has already been isolated and put in a common cold virus [sciencenews.org]!!!

      "...Nabel's team worked with intact blood vessels taken from people and animals. The researchers infected those cells with a cold virus they had engineered to carry the Ebola glycoprotein gene. Within 48 hours, massive numbers of endothelial cells began to die and the blood vessels became leaky. Such effects could lead to the internal and external bleeding caused by Ebola...."

      Kinda makes you wonder where ol' Nabel's virus is now, huh? Hope it's safely in the bottom of his lab freezer. But inserting the Ebola glycoprotein in a bacterium (as opposed to a virus) is basically a science fair project these days, so ANYBODY can get in on the fun. Who knows, the next Jack in the Box E Coli scare may very well be a version with an Ebola gene in it. The basic data you need for such a project is onlione at the SWISS-PROT [expasy.ch] database in Switzerland; just enter ebola in their search engine and see for yourself. The specific data for Ebola glycoprotein is here [expasy.ch], and in case that gets slashdotted, the relevant sequence data info is as follows:

      MGVTGILQLP RDRFKRTSFF LWVIILFQRT FSIPLGVIHN STLQVSDVDK LVCRDKLSST NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE AGEWAENCYN LEIKKPDGSE CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD FAFHKEGAFF LYDRLASTVI YRGTTFAEGV VAFLILPQAK KDFFSSHPLR EPVNATEDPS SGYYSTTIRY QATGFGTNET EYLFEVDNLT YVQLESRFTP QFLLQLNETI YTSGKRSNTT GKLIWKVNPE IDTTIGEWAF WETKKTSLEK FAVKSCLSQL YQTEPKTSVV RVRRELLPTQ GPTQQLKTTK SMASENSSAM VQVHSQGREA AVSHLTTLAT ISTSPQSLTT KPGPDNSTHN TPVYKLDISE ATQVEQHHRR TDNDSTASDT PSATTAAGPP KAENTNTSKS TDFLDPATTT SPQNHSETAG NNNTHHQDTG EESASSGKLG LITNTIAGVA GLITGGRRTR REAIVNAQPK CNPNLHYWTT QDEGAAIGLA WIPYFGPAAE GIYIEGLMHN QDGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT CHILGPDCCI EPHDWTKNIT DKIDQIIHDF VDKTLPDQGD NDNWWTGWRQ WIPAGIGVTG VIIAVIALFC ICKFVF

      Any genetic engineer worth her salt should be able to take this data and create a Ebola / E Coli hybrid plasmid with the help of this data and a friendly mail order supplier of synthetic DNA...

      Worried yet? I am. PS to any Fed reading this: don't worry, I'm no terrorist, I'm posting this in the spirit of Paul Revere, not Osama. The public has got to be EDUCATED about the implications of transgenic research and just how easy it is to do some really scary things that may well lead to the next 9/11...

      • Ebola's a really scary one, too. not because it's a particularly smart virus, quite the opposite. In evolutionary terms, something which destroys its environment so quickly is totally sucky. HIV is obviously much smarter, with a huge gestation period and good infectivity. Ebola has the potential to spread very quickly and visibly. Thus, a city gets quarantined, but not before everybody is infected. HIV ain't so good, cause it might take ten years to blow up in your face. Ebola is ore easily controllable once contained. It's like a clean nuke. Handle it right and it's a serious piece of evil fucking hardware.

        I'm afrad of the big bad wolf

      • At least with such quickly killing viruses the potential for spread is limited as the person doesn't have time to travel widely as a carrier...

  • A new virus?! (Score:5, Funny)

    by Schmelter ( 563031 ) on Thursday July 11, 2002 @09:09PM (#3868233)
    Great, another computer-engineered virus.

    No wonder my roomate has been screaming "I send you this file in order to have your advice. See you later. Thanks. " while throwing porn at me and defacing my website. Fortunately, I was able to powercycle him with a car-battery.

  • Oh great... (Score:4, Funny)

    by Anonymous Coward on Thursday July 11, 2002 @09:10PM (#3868237)
    Damn script kiddies designing their own viruses, how long until they get their own downloadable virus construction toolkit?

    What's it called?

    9o7i0

    kewl! I just made 5m4L7p0x

    Release it dude!

  • Ask Slashdot (Score:3, Interesting)

    by cDarwin ( 161053 ) on Thursday July 11, 2002 @09:25PM (#3868310) Homepage
    Question for molecular biologists in slashdot land:

    How hard would it be to reduce this to a stepwise procedure that any reasonably intelligent, resourceful, dedicated person could carry out?

    Making LSD from scratch required a lot of skill. But with detailed how-tos now widely available, practically anyone can make acid.

    • It's Hard (Score:5, Interesting)

      by krmt ( 91422 ) <therefrmhere@yah o o . com> on Thursday July 11, 2002 @09:47PM (#3868415) Homepage
      This would be a major, major, major pain in the ass to reproduce.

      Doing this kind of work takes a lot of time and skill and equipment. It's not particularly hard to get the stuff, but you do need stuff, and the knowledge to go about doing it, and you're not just going to get that knowledge from nowhere.

      This team worked for 2 years on this, and they are dedicated scientists with plenty of experience in this sort of work. How long would it take one person working in a home lab to start from scratch? Well over two years. If they don't know anything about Molecular Biology besides what they got out of high school (like your LSD-making example) probably at least triple that.

      Everyone is very paranoid about the synthetic virus thing. This is hard work. No, what's more scary is the technology that's been around for three decades or so now, which is the ability to modify existing viruses. Why would someone really go to the trouble to make a new superbug from scratch when they can just use what nature's already done?

      Or do you think that you can do a much better job than evolution has over millions of years?

      Not that there aren't problems with creating superbugs (even Ebola and HIV have major weaknesses) and it wouldn't be easy, but it'd be far easier to modify something that already exists than it would to build something from scratch.

      • Re: high level (Score:3, Insightful)

        by fferreres ( 525414 )
        Now it all looks like low level "programming". How long until there's enough research so that scientists can start using high level languages for this?

        It may sound stupid, but that's also what some hackers though about C or anything 20 years ago. Or even now (compiled vs. interpreted).
        • The way these scientists did this was actually fairly "high level". They ordered premade genes (read: libraries or objects) from the mail and pieced them together correctly. Obviously there's a lot more to it than that, but that's the gist of it. The problem is that it still takes a lot of skill and knowhow, as well as time and energy to do this.

          No matter what, you're still going to be cutting up DNA and splicing it together using enzymes.

          No matter what, you've got to make sure you have enough DNA, which means either amplification by PCR or growing it up in cells and isolating it.

          No matter what, you need to confirm what you've got, which takes more enzymes, gel equipment, and a good working knowledge of the sequence.

          No matter what, you'd have to package it in to a virus, something that's not easy even with today's kits.

          All of this can be done using "high level" stuff, kits for PCR, cloning, amplification, and isolation exist. You still need to understand what's happening, unless someone sends you a ready-to-make polio kit, you still have to know how to use the stuff. Having all of these tools lying around won't make the virus the same way having a copy of the gcc won't make you a programmer. You have to know how to use the tools.
          • I really meant "high level". As an example (imposibly simple and uneducated, but to ilustrate the point):

            <?php
            // As high level as it gets

            include "ebola.db";
            include "hapinnes.db";

            $replication = grow(stablilize(splice(ebola.dna, 5, 7, soup(5,7,12))));
            if($hash = confirm($replication)) {
            simplify($replication, MatterLaw_Method5(4,$hash));
            } else {
            echo dump_analisis($replication);
            }
            $done = complement(replication => $replication, * => $hapinness);
            package($done);
            print($done, "DNA_Printer1", 50);
            ?>

            Or nothing at all can be abstracted?
            • You're very right, biology can be more abstracted, up to a point. If someone decided to place a bunch of virulent genes on a single plasmid, or just took one from one of the bacteria that already have them, and simply put a multiple cloning site (a piece of DNA that can be cut in multiple different ways easily) in to it and sold it, there's a real big problem for everyone. Then the person using it isn't much better than a script kiddie, but yes it could certainly be abstracted in that way so that the person wouldn't have to know jack.

              But no matter what they'd have to have some basics down, like how to run a gel or transfect bacteria. Not hard stuff, but they'd have to know how to do it. The more and more stuff people build up, like the antibiotic resistance example, the more abstract it can be, just like today you don't have to write to the hardware, you can use something like Perl. They'd still have to learn the equivalent of Perl to do it, which is no small task in itself, but even today there's no need to go around isolating your own restriction enzymes and such.

              It is very much an engineering question, just like in software. The more complex your library is, the less you have to worry about. There's a lot of premade stuff out there that can be pieced together already. We're not really at scripting language level, but we're well beyond assembly. Things can be absracted, but only to a point. Like if you want to write your own OS, you can't really do it in Perl (or perhaps bash is a better example there, perl is an organism unto itself ;-), and no matter what you're going to have to get down to some assembly at some time or another. Same thing with this. You can do some very basic things now, like make bacteria turn blue, which many high school biology classes do each year (the technology is over 25 years old!) but to do something as complex as synthesizing polio from scratch requires really knowing nuts and bolts. It's all a question of how much you want to do. Something simple? Doesn't take much knowledge. Something really tough? You'd better really know what you're doing.
        • It doesn't sound stupid. I watched the local University channel one day out of boredom and they were discussion how gene's are processed. I understood the PROCESS immediatly, the terminallogy, etc was new to me, and I must admit quickly forgotten. But the process itself made perfect sense. Meanwhile, the professor asks the class a question and they stared back blankly like the whole thing was beyond them. It probably was. They can memorize all the molecules, etc they want. But I doubt most of them can understand a process in the same manner as most programmers do. I think a mix of molecular biologist & computer programmer will be the scariest thing in the next 20 years...

  • Spit Kiddies! (Score:2, Funny)

    by tchdab1 ( 164848 )
    Now we'll get hassled by spit kiddies - anyone that can follow a sequencing recepie will be generating these things.

  • This frightens me badly. Judging from the success that the FBI have had at tracing certain people involved in last year's Anthrax spree (at least one of the suspects was involved in biowarfare trials against blacks in South Africa in the '80s), I shudder to think what one pissed off reseacher could do and how the inept security agencies would not be able to do anything about it.

  • They *think* they made an exact copy... (Score:4, Interesting)

    by pstav ( 589582 ) on Thursday July 11, 2002 @09:52PM (#3868429)
    But a slight change in the molecular make up of the man made Polio renders this new virus unrecognizable to the antibodies devoloped by the Salk vaccine.

    Be very afraid...

    • Why do you say that?

      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).

  • Methods not suprising (Score:5, Insightful)

    by rockrat ( 104803 ) on Thursday July 11, 2002 @09:56PM (#3868446)
    That these scientists downloaded their instructions off the net and used ordered the sequence mail order is not at all the shock that this story portrays it as. Virtually every common technique in molecular biology can be accomplished with a pre-made "kit" from one of several major vendors (e.g. Sigma [sigmaaldrich.com], BioRad [biorad.com], Qiagen [qiagen.com]). These kits contain all the necessary reagents and instructions for completing the procedure. Most of the companies that produce these kits also post the instructions on their websites in case you loose the printed copy. Any trained molecular biologist would have a pretty easy time recreating the "kit" from the directions and the ingredient list.

    As for getting DNA by mail, that's standard practice at most research labs I've been involved with. It's more expensive than producing it yourself, but a hell of a lot more convenient. Many universities even have their own, "in house", sequence generation facilities that labs interact with by, you guessed it, inter-departmental mail.

    I'd say the poster of this story was taken by the shock value of these statements (and perhaps they are more shocking in our terrorist-paranoid times), but in reality, there's nothing to be suprised by.

    • Re:Methods not suprising (Score:4, Informative)

      by genesplicer ( 314591 ) <sbuttars AT gmail DOT com> on Thursday July 11, 2002 @11:13PM (#3868707)
      Getting DNA by mail certainly is standard practice these days ... Some of the suppliers I've dealt with in the past include IDT [http://www.idtdna.com], Oligos Etc. [http://www.oligosetc.com/], and Operon (a subsidiary of Qiagen) [http://www.operon.com/] ... Orders are accepted by phone, fax, or email - have your credit card ready (I'm being totally serious) ... Plus there's usually even locally owned and operated "Mom-and-Pop" style oligo shops around where there's a market ...

      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 ...

    • That these scientists downloaded their instructions off the net and used ordered the sequence mail order is not at all the shock that this story portrays it as. ...
      Any trained molecular biologist would have a pretty easy time recreating the "kit" from the directions and the ingredient list.

      Well, that's the whole point - it's not difficult to do, and someone has finally done it. Terrorist groups can assemble their own viruses - no need to gain access to actual viruses which may be tightly controlled.

  • More details at Science and Nature (Score:4, Informative)

    by mallorean ( 410993 ) on Thursday July 11, 2002 @10:05PM (#3868485)
    Science [sciencemag.org] (subscription required)and Nature [nature.com] have more details. The citation of the paper is

    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).

  • Is it really from scratch? (Score:3, Insightful)

    by leighklotz ( 192300 ) on Thursday July 11, 2002 @10:09PM (#3868501) Homepage
    I can understand that the virus was created from scratch in the sense they it didn't come from mammalian cell infected by another polio virus, but my guess is that it is not from scratch in the sense of making a biological thing out of stuff from a chemistry set, because the "reagents" used in the process almost certainly had biological origin in their manufacturing.

    Can someone familiar with the process comment on the source of the reagents?
  • biologists have been able to insert additional genes and knock out genes in organisms for quite a while. while this is the first time they've completely synthesized a virus, as real geeks of course you know that reinventing the wheel might be a good exercise but is hardly ever the most efficient way of reaching a goal - a bioterrorist / military would therefore never build a virus from scratch to use it as a biological weapon but use a perfectly working virus from the wild that already has the ability to infect human cells and maybe alter it to reach the "desired" effect. the techniques needed for that have been the microbiologists' bread and butter for years.

  • Shades of Jake Brundlefly (Score:3, Funny)

    by gelfling ( 6534 ) on Thursday July 11, 2002 @10:12PM (#3868510) Homepage Journal
    Do it yerself gene sequencing...ooops
  • in my AP Biology class we made a strain of e.coli that was resistant to the antibiotic ampicilin. That was pretty fun. We also got them to turn green when they broke down lactose (or glactose...which ever is bigger...i forget).
    I guess this is more impressive though. I want to be a bio major in college, so i hopefully will get to do some neat stuff like this.
  • Sounds like the script kiddies of the microbiology world.

    They just took ready-made, off the shelf parts & put them together
  • I have a depressing feeling that my body is less secure than old Outlook Express, yet I cannot upgrade it. Until we have a patch, the vulnerability should not be disclosed :-)
    • Not at all, you have multiple security monitors/tripwires/firewalls/virus scanners running. The human immune system is fiendishly complex and quite ferocious.

      Now, you can't upgrade the OS without trashing your filesystems, which is kinda sad, and there's no viable backup mechanism...

  • Did these guys create "life"? (Score:3, Interesting)

    by VValdo ( 10446 ) on Thursday July 11, 2002 @10:30PM (#3868561)
    There is an ongoing question [beyondbooks.com] of whether or not viruses are "alive". Clearly the fragments of DNA used to reconstruct the polio virus aren't, right?

    If the "frankensteined" (a good word here) polio virus replicates and acts in other ways like a regular virus...

    Did these guys create life from lifelessness?

    W
    • The reason this question has not been settled unanimously is because it is a flawed question. "Life", just like any other definition, such as "America" or "body" or "good" is just a definition. There there a true "essence" that defines "life" to make it absolute. Some consider the entire earth to be a living organism (Gaia). Some consider the entire universe to be an organism (God). Some consider nothing to be alive, but just atomic processes exhibiting emergent phenomena, and the definition of life is an arbitrary boundry.

      There is not an absolute definition of life... We are asking to define life by deciding whether a virus is alive or not.

      LS

  • Mail Order Gene Sequences (Score:4, Funny)

    by CaptainCarrot ( 84625 ) on Thursday July 11, 2002 @10:49PM (#3868616)
    They should be very, very careful. You never know what might happen [sluggy.com] with mail-order gene sequences, or genetic material from eBay [ebay.com] or such places.

  • Can't stop science (Score:2, Insightful)

    by nukeade ( 583009 )
    As scary as this is, and for all the negative implications it has, I have to say that the research must continue, the reason being that it may lead to something positive in the future, such as a universal cure for virii. Remember what happened to Britain before WWII? They banned civilian explosives research and so when the time came Germany was massively far ahead. In the same way, the civilized world must continue their research so that hopefully the good guys have the answer before the bad guys have the problem.

    I just hope I have the good guys and the bad guys straight. Deus Ex was a great game, but I sure don't want it to be real.

    ~Ben
  • Corewars [corewars.org]

    and

    More Core Wars [koth.org]


    and

    Even More Core Wars [sourceforge.net]


    Okay, not virii - but still programs that kill each other are kinda cool :-)

    Whats more is people are evolving [geocities.com] these little programs to be better.

    Oh they have a newsgroup [rec.games.corewar] too.( google alt.rec.corewar [google.com] )


    /op
  • I'm no virologist (or biologist for that matter), but it seems to me that there is nothing to fear here. Why would a bioterrorist "do it the hard way" when there are plenty of naturally ocurring and lethal pathogens out there? In fact, this kind of biotechnology is our best hope of a real defense against such weapons.

    Biological warefare was practiced in ancient times. Even though they had no real disease theory, they know that hurling diseased corpses into walled fortifications would spread disease. They new that fouling water upstream of a city would spread disease. They did all this with no scientific knowledge of biology or pathology whatever.

    Bombs are easier than bugs. Planes are easier than missiles. Radiation and disease are only probable attacks because of the primal fear they create. Biotechnology offers the best hope of defense against the latter (and maybe even a cure for the effects of the former). We need to know much more, sooner, not later.

  • Smallpox Virus (Score:3, Interesting)

    by xSterbenx ( 549640 ) on Friday July 12, 2002 @12:56AM (#3869092)
    The funny thing, the sequence for smallpox has been available for quite some time at NCBI (National Center for Biotechnology Information [nih.gov], as are the sequences for at least 2000 viruses and phages (per my last count).

    I'm all for public knowledge of such sequences if they lead to productive research in the areas of disease control. However, with the current technology of being able to construct viruses from sequence data, it might be prudent to restrict such data to only respectable research centers.
  • I see it happening every weekend in NYC, but I'm sure it happens elsewhere. Let me explain my findings.
    I've found that people between the ages of 19 to 30 are most likely to be infected by this virus. It usually always happens after drinking at bars or clubs. I even have been infected by this dastardly virus. After having quite a few beers and vodka cranberries, I've been know to get infected by virus that I've been calling the ILOVEYOU virus...It's usually only communicable to people of the opposite sex, unless you travel to the village. The more you drink, the more apparent this virus becomes. Good thing is that it usually lasts only about eight hours before it's effects wear off.

    I'll get to the bottom of this. Will report back with more information on Sunday.

    - grunby
  • IWAMB (I was a molecular biologist, until I discovered programming paid better, at least before the last round of layoffs...)

    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
  • It'd really suck if the /. crowd worked out how to make their own Virus...

    (http://www.access-music.de/)
  • .. make me want to paint monkeys on the walls, pluck out my teeth and travel to and from the past?
  • Okay, why the f*ck did they use polio? Isn't there something more benign they could have messed with? Crap.

    [2 scientists smoking crack]
    Scientist 0: What should we make?
    Scientist 1: How about Ebola?
    Scientist 0: Too 'Tom Clancy.'
    Scientist 1: Hmm. Smallpox?
    Scientist 0: Nah. E-Coli?
    Scientist 1: Not cool enough. Anthrax?
    Scientist 0: Been there, done that.
    Scientist 1 & 0: [at once] Polio!

    You have to wonder what the crap goes through these guys minds. I mean, how is this a good idea? I'm all for scientific research and stuff, and yeah I know some of it is dangerous. But this seems to be tempting fate to me. What's the matter with making something *benign*?

  • I do have my own gene sequencing mail order company. I work for Northwestern University in the Chicago campus in a molecular bio lab and let me tell ya, I still remember the first time I designed 20 sequences, sent off a long list of a's c's t's and g's online and got tubes of them back in five days. I felt like a god.

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