Chuck Darwin posed a very good question here that I’m spinning off into a new discussion.

The work Taubenberger and others are doing on the evolution of influenza a century ago is fascinating and could very well be pertinent to prediciting future influenza virus genetic drift/shift, host-virus interactions, etc. However, I ask myself if the benefits of this work for future public health, as well as for general scientific interest, is worth the risks when it comes to biosecurity. With reverse genetics methods introduced a few years ago, any influenza virus can be generated through relatively common, albeit cumbersome, molecular biological techniques. For someone with a solid background in molecular biology and the ability to read the average materials and methods section, it would only take the proper resources to generate any strain someone wanted.

This concern extends to other viruses. I have a real problem with the sequence of smallpox being determined and made publicly available, as, once again, tedious but straightforward cloning techniques are now available to, in theory, produce smallpox virus “from scratch”. In short, I am curious what everyone here thinks about these issues. Is the human “need to know”, a trait that is particulary strong in scientists, going a little too far in some facets of biology? Should the virology community be making a greater effort to discuss the ethical and security implications of their work? Self-regulation in the early stages of recombinant DNA technology was very impressive. Have we lost our way while technology speeds forward?

spudbeach already responded in this comment and Dior here; I’m putting my thoughts below the fold and welcome comments from everyone else.

I’m much less concerned about the Spanish flu sequence falling into the hands of bad guys than I am about something like smallpox. H1N1 influenza viruses have been circulating in the human population now for many years, so it’s hard to say whether, even if it was reconstituted by someone intending to do harm and released, if it would have the same effect as it did in 1918. You’re probably also familiar with the work done on recombinant mousepox, where they found that by inserting the IL-4 gene into the virus, it made it more deadly. (News story on it here for anyone interested). If people have the technology and training to make viruses from scratch using reverse genetics, they probably also have the ability to create crazy stuff like the deadly mousepox (or something else that we’ve not even thought about). All kinds of things have the potential to be used by terrorists if they’re clever enough; I hate to see limits put on our knowledge or publications because of the risk that they might be used by the wrong people.


  1. #1 Rob Knop
    July 28, 2006

    I hate to see limits put on our knowledge or publications because of the risk that they might be used by the wrong people.

    If you outlaw knowledge, only the outlaws will have knowledge….

  2. #2 trrll
    July 28, 2006

    It’s worth noting that the guys who did the IL-4 work weren’t trying to create a superdeadly mousepox–it was an unanticipated outcome. So what if they had declined to publish? I think that I’d be more worried to have this kind of knowledge floating around privately than to have it published and make everybody aware of the hazard. At least this way if some super nasty pox variant pops up, we’ll know to be on the lookout for interleukin genes.

  3. #3 Chris
    July 28, 2006

    I’m less concerned about smallpox than about some new threat, anyway. Sure, there are lots of people now that aren’t immunized against smallpox, but we know how to deal with smallpox if we have to.

    Smallpox isn’t that frightening as a biological weapon because it’s a *known* disease that we already have ways to deal with.

    The implication is clear: a known threat usually has known defenses, and thus, is less of a threat.

    Furthermore, while someone could produce a complete set of smallpox _DNA_ (or is it RNA? Some viruses are, I think) from scratch, that would not be a working virus capable of infecting cells. Loose DNA would just get gobbled up by the nearest macrophage. It needs the whole assembly of the virus body to allow it to invade and infect a host cell, and while the body is (theoretically) implicit in the DNA, it may practically be a lot more difficult to produce it and get it to assemble into the right configuration with the viral DNA on the inside than to synthesize the DNA from scratch.

    I seem to remember hearing that in some cases the viral DNA doesn’t even code directly for the virus’s body proteins or enzymes; it hijacks some of the host’s proteins or even (I think) cuts up the host’s DNA and stitches it together to produce a new strand that codes for something important to the virus. Throwing the viral DNA in a test tube with some ribosomes isn’t going to produce that.

    You might as well say that the Human Genome Project has solved the problem of human cloning: anyone who wants can just sequence the DNA of a complete human. DNA is an important part of life, but it isn’t the _only_ part.

  4. #4 David Harmon
    July 28, 2006

    Chris: excellent point. In general, I’d lean towards publication on the principle of arming the “good guys” as well as the “bad guys”. I might respect some exception for something especially threatening, but the real problem is, that sort of secrecy can delay hostile use, but not necessarily stop it. These days, the bad guys can increasingly do their own culturing, or even sequencing.

    So, if you try to make a secret of the genome for, e.g., Ebola, then the Terrorist du jour could just send one of his suicidal flunkies down into Africa to get a sample. And when he releases his superhardy, air-contagious version, the medical labs don’t have a sequence to compare it to. Even if they immediately get the sequence hand-delivered from the Secret Government Vaults ™, they won’t have the insights they would have gotten from months or years of studying that sequence when there wasn’t a crisis going on! I’d much rather have a generation of biology and medical grad students musing over pizza: “so, if Ebola really busts loose, just what could we do about it?…” That way, when it does, there are people scattered through the field who’ve actually thought about the issues beforehand.

  5. #5 Chuck Darwin
    July 28, 2006

    Thanks for expanding this discussion Tara! I asked the question as someone who is truly conflicted, not as someone who has already made up his mind that repressing information or limiting the scientific endeavor is the right choice. In fact, if asked to decide this minute, I’d certainly go with “let everything stay out in the open” before advocating any sort of limits. I just figured it would be a good chance to pose the question. I do believe, however, that the ever-expanding life sciences community should be doing a better job of setting up ethical guidelines on many issues. The seemingly never-ending reports of scientific fraud are truly alarming (it’s hard to go a month of reading Science or Nature without seeing some article retracted due to fraudulent data). The extremely competitive nature of science, especially with academic positions at a premium, and the lack of oversight of laboratory personel by P.I.s with too much ego and money, has really put at risk the reputation and integrity of “scientific research” as a whole.

    Chris, smallpox is a large DNA virus. You make a good point about the difficulty one would have making fresh smallpox “from scratch” as I proposed. Poxviruses incorporate a number of viral enzymes into the virus particle itself that are required for initial replication in the infected cell’s cytoplasm. However, by using commonly available poxviruses like vaccinia in a helper-like role, it remains feasible (as far as I can tell at least) to generate the virus just with knowledge of the genomic sequence.

    Tara, you make a very good point about how clueless we are about what sort of immunity today’s population would have against the 1918 influenza virus. What is worrisome, however, is that pathological findings using the surface proteins of the 1918 virus in combination with a common flu “backbone” have demonstrated that the 1918 virus does possess a striking ability to cause tissue damage in the lung that is not seen to such an extent in most other viruses that have been isolated, including other H5N1 viruses.

    I appreciate all the thoughtful comments.

  6. #6 Chris
    July 31, 2006

    Ah, I hadn’t thought of using a related virus as a body.

    Nevertheless, I think any organization smaller than a government is unlikely to have the resources to carry this out at all; but if they did, stealing the genome is likely to be *much* easier than creating the virus given the genome.

    Some people seem to have the unfortunate belief that secrets *stay* secret; they generally don’t.

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