Jeffrey LewisSynthetic Biohazard Non-Proliferation

Hey buddy? Wanna a good deal on gene?

The advertisement (right) is not science fiction.

Blue Heron Biotechnology of Bothell, Washington “can synthesize any gene regardless of sequence, complexity, or size …”

Gene synthesis is a revolutionary technology, which offers the prospect of making life better for millions of people around the world. The ability to order the exact gene would revolutionize the production of vaccines and the creation of tiny bio-machines.

But what if you wanted to cook up some synthetic polio in the lab?

You can do that, too.

A group of researchers from SUNY Stoney Brook synthesized polio over the course of three years. Blue Heron claims it can perform a similar size job in a little under 12 weeks.

Terrified yet? In 2003, a CIA Report entitled The Darker Bioweapons Future warned that advances in biotechnology “could be used to create the world’s most frightening weapons.”

Blue Heron has refused orders that seem suspicious—for example, Blue Heron turned down an order from Saudi Arabia for a variola gene related to smallpox—but not all manufacturers of synthetic genetic material screen purchases.

The process is called oligodeoxyribonucleotide synthesis—“oligo synthesis” for cocktail party conversations where you somberly warn of the threat from “oligo terrorism” before excusing yourself to refresh that G&T.

Harvard Medical School’s George Church proposed establishing a voluntary DNA Instrument & Reagent Registry to establish licensing and screening proceedures.

John Mulligan, CEO of Blue Heron, has some ideas, as do Chris Chyba and Alex Greninger.

More generally, several papers outline oversight regimes to allow the life sciences to proceed safely, including the National Academies’ Biotechnology Research in an Age of Terrorism and a paper by my CISSM colleagues entitled, Controlling Dangerous Pathogens: A Prototype Protective Oversight System.

Fascinating, if terrifying, stuff.


  1. JLo (History)

    Not unheard of, though, and not necessarily sinister. Church seems to be on the right track, though it’s unlikely we’ll ever know all the experimentation going on in the shadows.

  2. alek (History)

    Hi Jeffrey.
    these things have been there for quite a while. The thing is that in reality it is really hard to make anything that scary. The easy things with short sequences are available in nature so it is way easier to get to Africa or Northen Russia and get Ebola or tularemia.
    The hard thing (Smallpox), is way more complicated than just plug-and-play.
    I’ve been on that seminar when UMD presented all the papers you reference. But my understanding is that we have a wrong attitude – we should not say “You can do that, too.”
    I can’t…I mean I am in the bioengineering and still.
    Also, here is another paper on that topic, do not take it as a self advertisment 🙂

  3. mark gubrud (History)

    Alek’s assessment of the state of the art matches my own, and it is important to understand that no single “breakthrough” advance, such as the ability to synthesize whole genes, is likely in itself to represent a discontinuous advance in bioweapons technology or proliferation potential. For example, polio is a relatively easy case, a relatively small virus, and viruses are relatively easy because they are not metabolic and you can get active virus by just mixing its parts together in a test tube.

    On the other hand, there is a fundamental issue here: looking ahead a few decades, it seems likely that the accumulation of many advances constituting the whole art of biotechnology will mean that the technology will be available (and, it seems likely, widely-available) to synthesize not only a wide range of naturally-occurring pathogens but also their genetically enhanced variants and entirely new lethal creations, cocktails of the dirtiest tricks of several natural pathogens and even new, custom-designed molecular mechanisms.

    Such engineered plagues would probably overwhelm the best public health and biodefense measures available today. Whether they would overwhelm the defenses available at the time, or whether biodefense can catch up and keep pace with the advancing and proliferating offense, is an open question.

    It doesn’t seem to me that we’re well prepared today for what a moderately competent bioterrorist (note that we’re not talking about a malevolent teenager here, but someone, or probably a group with training, experience, funding and access) could do today with anthrax (using widely available materials and equipment).

    I suspect it will remain the case that bioterror attacks on major urban areas could kill lots of people, but that the resulting plagues could be contained by the combination of physical isolation and biomedical measures. Thus the threat of bioterrorism is not going to go away but neither is it likely to escalate to an existential threat, at least not due to the action of the bugs themselves; social, political, economic and military reactions to bioterrorism are another matter.

  4. alek (History)

    It’s true, I agree with Mark that it is certainly a future threat and he is right that it is a moderate threat.
    Any pathogen that may potentially be developed in next ten years will most likely be a combination of the existing ones at very best. If so, then we already have vaccines and means of detection. Thus I agree that “but that the resulting plagues could be contained by the combination of physical isolation and biomedical measures”.
    Potentially there is a threat of overcoming the smallpox vaccine, but I think it is extremely hard task and is very unlikely in foreseeable future.

    It does not mean that no measures have to be taken, instead, I myself called for measures to limit the access to the facilities for genetic manipulations. My point is that we should not overestimate the threat.
    By the way, it is a very interesting site and I want to thank author for supporting it.

  5. Anthony (History)

    Having a genetic sequence doesn’t mean you have an organism. We barely have the understanding to reconstruct organism by slightly tweaking it’s natural life cycle. (eg. the SUNY Polio)

    Just because you have a sequence doesn’t mean the sequence is actually functional. Making it functional as living thing to do all the wacko evil things is BEYOND our current technology.

    (eg. what happen if we have airborn influenza but with AIDS potency)

    Microbiologist will give you a blank stare. That’s like asking current rocket scientist to build intergalactic rocket.

  6. dave

    Not to sound like a chicken little, because I do agree with what both Alek and Mark have said, but I would like to provide a counterpoint for discussion insofar as pointing out that the most likely versions of ‘novel’ (actually hybrid) bioweapons will arise from the co-opting of laboratory research into viral vectors for gene therapy; this requires not any excessive work other than to build on what others have already created for good, and some moderate virology/molecular biology skills. Most of these vectors come with great promoters, particular tropism, etc. that could be leveraged for evil rather than their original medical intent. Adenovirus encoding (insert your favorite/most feared toxin here)?
    Tactical…yes, because rather than propagating uncontrolled, these vectors are often self-limiting; probably limited to fancy toxin-encoding delivery systems, but still quite threatening (particularly for the general populace), I’d opine.
    Even vaccinia, which more and more research labs are using (as a vaccine vector for other genes, even if not for biodefense research, per se) is easy enough to modify, and so by my thinking, we should also be grateful no one has fielded a vaccinial threat inclusive of the human IL-4 gene (attempting to replicate the ectromelial work of Ramshaw et al in people).
    Thanks much to the ACW folk(s), btw. Appreciate your blog greatly.

  7. alek (History)

    That is true, I thought about this possibility as the most likely case too. Current vectors have specific part cut out so they can’t proliferate in humans, meanwhile, it is possible for a group of scientists to make that piece and insert it back.

    Now we have a vehicle for say…shRNA or other things you are talking about.
    Still it will take a while and a LOT of efforts to make it really dangerous, but I think it is possible. Now the questions are: can we detect this thing? The answer would be yes if we can detect the vector itself.
    That one I do not know, but it is possible.

    Can we cure it? Well, I do not know, that’s a hard one. Depends on the detection time.

    The last one – how much efforts will it take to make one without being undetected? A LOT.
    That’s the tought part as one would have to do a number of different trials and hope for success without any guarantee, then, one would have to test it in the laboratory on humans. Tough thing.
    But possible. I had that thing in one of the presentations at MIT. And I agree that we have to take measures in advance here.