Synthesizing Bioterror

Are mail order pandemics in your future?


Want to create a pathogen? Just download its gene sequence information from the Internet and place an order with a gene sequencing company. The genes arrive in the mail a couple of days later. Mix it in your basement lab and then release on an unprotected public. Is this nightmarish vision of mail-order bioterrorism really possible?

Most experts agree that basement bioterrorism is unlikely right now. But rapid improvements in the technologies that allow researchers to generate genetic material starting from just information and raw chemicals could make such bioterror attacks possible in the next decade or so. The synthesis of entire viral genomes—the complete set of genetic information of these microbes—has already been done by legitimate researchers.

For example, in 2002 one team constructed the polio virus us­ing only published DNA sequence information and mail-ordered raw materials. In 2005, another group similarly reconstituted the 1918 pandemic influenza virus that killed tens of millions of people.

DNA synthesis is now a billion dollar business. Currently there are at least 25 companies in the U.S. and 21 others around the world that are capable of manufacturing gene-length stretches of DNA. And the cost and ease of gene synthesis has fallen more than 50-fold and is halving every 32 months. In addition, 15 firms in the United States and seven foreign companies sell new or refurbished DNA synthesizers. Tens of thousands of these machines have been manufactured and are widely available. Used ones have been offered eBay.

The burgeoning field of synthetic genomics promises vast new possibilities for curing disease and producing new eco-friendly products and services. However, like all technologies, synthetic genomics can be abused. In June, this concern was addressed by researchers in an article in Nature Biotechnology, "DNA synthesis and biological security." The researchers made three broad recommendations, i.e., researchers ordering synthesized DNA must identify themselves and their institutions to the companies from which they are ordering sequences; companies should use software to screen orders for suspect sequences; and sequence manufacturing companies should work with government agencies to establish a system for alerting officials to suspect behavior.

The researchers also highlighted proposals that they believed would be impractical. These included limiting access to material, equipment and know-how; restricting access to information about pathogenic DNA sequences; and, checking all DNA sequence orders through a centralized government clearinghouse.

In October, a private initiative by the J. Craig Venter Institute, a Washington, D.C.-based think tank, the Center Strategic and International Studies and the Massachusetts Institute of Technology released a new report specifically focusing on the dual-use concerns of synthetic genomics, i.e., the construction of functional organisms at the lab bench from scratch. The report, Synthetic Genomics: Options for Governance (Venter Report) aims at preferred policy solutions that "both mini­mize the risks from nefarious uses and mini­mize the impediments to beneficial uses of the technology."

How fast do researchers and policymakers need to move to prevent synthetic genomics from being abused? The good news is that the best judgment of the researchers is that synthesizing pathogens like the smallpox virus is still too complicated for would-be bioterrorists. For the near-term, bioterrorists are more likely acquire pathogens the old-fashioned way, by stealing them from labs or isolating them from the wild. However, the report takes "as a given that now, or within a few years, any virus with a known sequence can or will be able to be constructed in a relatively straightforward manner."

The Venter Report researchers identified three major points for policy intervention; commercial firms that sell synthetic DNA; owners of bench-top DNA synthesizers that can make their own DNA; and, researchers who use of synthetic DNA themselves.

At the point of DNA synthesis, the researchers suggest that all DNA synthesis companies use software to screen orders for suspect sequences. Such suspect sequences can be found in databases such as the Lawrence Livermore National Laboratory's virulence factor database and the National Select Agent Registry. The majority of sequence manufacturing companies already do this, so it should not be a problem to extend this requirement to the remaining companies.

Another possible safeguard would require that institutional biosafety officers certify to DNA synthesis firms that the people ordering sequences are legitimate researchers. This would make the research institutions where scientists work rather than DNA synthesis firms responsible for verifying legitimate users. Once a scientist had been certified as a legitimate user, the biosafety officer wouldn't have to screen each shipment. In addition, a list of approved researchers could be maintained and updated electronically so that individual orders could be approved with minimal time delay. As the report notes, this is procedure is similar to the approach used by the American Type Culture Collection (ATCC) which distributes biological materials such as cell lines, bacteria, animal and plant viruses. The ATCC only ships potentially hazard­ous material with the approval of a registered biosafety professional.

One other suggestion aimed at sequencing companies is that they keep a record of who orders what for a specified amount of time. This information could be passed along to police officials in the event of an incident.

What about those bench-top DNA synthesizers with which researchers can make their own gene sequences? One suggestion is that the synthesizers should be registered with a government agency so that each has a known assigned owner. A more stringent requirement would be licensing synthesizer owners, that is, only people who are approved by the government beforehand may possess such machines. Discovering that a machine is either unregistered or unlicensed would be an immediate cause for suspicion. An even tougher constraint would be requiring that everyone who uses materials associated with producing gene sequences be licensed.

The last point of policy intervention discussed in the Venter Report is the consumers of synthetic DNA themselves: researchers. Here the report makes a number of reasonable suggestions with regard to educating researchers and establishing cultural norms. These include educating young researchers about risks and best practices as part of university curricula; compiling a manual for biosafety in synthetic biology laboratories; and, establishing a clearinghouse for best practices. The report also suggests broadening Institutional Biosafety Committee (IBC) review responsibilities to consider risky experiments. IBCs exist at most research institutions though small private companies may have to seek outside evaluation of biosafety issues.

The IBCs could initially use the criterion established in the National Academy of Sciences' (NAS) 2004 report, Biotechnology Research in the Age of Terrorism to identify experiments that merit extra scrutiny. The NAS report named seven classes of risky experiments. Specifically, experiments that (1) demon­strate how to render a vaccine ineffective; (2) confer resistance to therapeutically useful drugs; (3) enhance the virulence of a pathogen or rendering a nonpathogen viru­lent; (4) increase transmissibility; (5) alter host range; (6) enable the evasion of a di­agnostic or other detection; and (7) enable weaponization. Earlier this year, the National Scientific Advisory Board for Biosecurity (NSABB) issued a proposed framework for the oversight of dual-use life sciences research that expanded somewhat on the NAS list of risky experiments.

Some of these suggestions are quite sensible and unlikely to slow down beneficial research. For example, using software to screen orders for suspect DNA sequences, maintaining a list of customers, and registering DNA synthesizers do not appear to be unduly onerous. Licensing proposals should be rejected. Licensing the purchase of research materials would in effect turn them into controlled substances. And the Feds are already notoriously slow in approving security clearances, so there is no reason to think that they will be any speedier when it comes to approving DNA synthesizer licensees.

A robust biotech research sector that is not hobbled by excessive regulation is our best defense against bioterrorism (and natural pathogens). Instead of being a threat to our safety, rapid progress in biotech will enable us to quickly identify pathogens, either man-made or natural, and create fast and effective treatments for them. The response to the 2003 SARS outbreak in which that virus' genome was decoded in two weeks and vaccines were developed shortly thereafter is a good example of how biotechnological progress can protect us.

Finally, as meritorious as some of preliminary suggestions for governing biotech research may be, do they really address what should be our main bioterrorism concerns? The Venter Report specifically sets aside any consideration of state-sponsored research. Most nations have ratified the 1972 Biological Weapons Convention (BWC). However, that treaty has no enforcement and inspection mechanism. Consequently, at least one BWC signatory, the Soviet Union, maintained a vast biological weapons program until its collapse in the 1990s. As for basement bioterrorism, it is far more likely to emerge some day from a far off cave in the wilds of Pakistan than from a California university laboratory.

Ronald Bailey is Reason's science correspondent. His most recent book,
Liberation Biology: The Scientific and Moral Case for the Biotech Revolution, is available from Prometheus Books.

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  1. Number 8 on the NAS Ten Worst list might be :

    ‘insert sequences which express proteins that yield illegal drugs as metabolites.

  2. The guys in the far off cave get my vote. It won’t be high tech. It will be massive. American policy is already giving our enemies the delivery system.

    Here is how they wll do it.

    Afghanistan is today the largest supplier of heroin to the free world. Americans consume some 18 tons of heroin a year and the government admits that 25-35% of it comes from Afghanistan. That is 4.5 to 6.3 tons of Afghan heroin being distributed onto American streets TODAY.

    One pound of pure heroin is more than 45 thousand 10-miligram doses.

    Afghanistan, according to the World Health Organization, has naturally occuring anthrax at endemic levels. All of those goat herds breed the stuff naturally. Afghanistan is also just a few hundred miles south of the former Soviet bioweapons research lab in Alma-Ata, Kazakhstan. A lab that stores hundreds of the most deadly bugs ever researched.

    So, access to deadly bugs is a foregone conclusion and access to a delivery system, already in place inside of America, is a given.

    All that alQaeda needs to do is contaminate five kilos of heroin and distribute those five kilos to five major American cities to instantly create one-hundred-thousand “patient zero” cases in each city. Such a massive attack using a common bug like anthrax would quickly reduce the American population by 20% within weeks. It would over-power our medical systems in days. Investigators trying to trace the source would be stymied by addicts reluctant to talk about their illegal sources thus making the spread even more aggressive.

    Anthrax presents itself in 12-14 days displaying cold like symptoms. A patient is infectous in 10 to 20 days. Five-hundred-thousand addict patient zeros each contacting and infecting ten other Americans who then each infect ten other Americans would infect 50-million Americans in the first month.

    Now consider these cases concentrated in our largest cities and industrial centers. Manhattan and L.A. for communications. Washington, D.C. Seatle’s Boeing plant community. The Texas coast cities with their concentration of oil industry and refining. Chicago’s distribution hub to the entire continent.

    As long as the United States government continues to prohibit the regulation of distribution of the intoxicant drugs to the $ 144-billion consumer demand in America the United States government itself gives alQaeda control of the heroin distribution into America as well as the money to buy the treason of any under-paid bioweapons technician in the former Soviet Union.

    And the U.S. government knows this.

    The 2006 National Drug Threat Assessment of the National Drug Intelligence Center of the Justice Department claimed success at reducing Colombian heroin and indirectly warned, in the heroin section of the report, that Mexican, Dominican and Colombian distribution channels into the U.S. would start to consort with Southwest Asian (Afghanistan) producers as Colombian heroin production declines.

    “Significant and prolonged shortages in South American heroin most likely would not result in an increase in distribution of Mexican heroin in eastern states because Mexico heroin production capacity appears insufficient to meet total U.S. demand and because users of white heroin have strongly resisted using black tar heroin. Instead, shortages in South American heroin availability would most likely result in an increase in Southwest Asian (Afghanistan) heroin distribution in U.S. drug markets; however, such distribution would very likely be controlled by Colombian and Dominican criminal groups who would purchase Southwest Asian heroin from sources in Asia or Europe.”

    Our success at interdiction in Colombia is driving the Colombian distributors to seek out Afghan suppliers. SUCCESSFUL U.S. DRUG INTERDICTION IN COLOMBIA IS CREATING THESE CONNECTIONS.

  3. My numbers in the above post are off by a factor of ten but the premise and facts remain. Sorry about any confusion.

  4. Thanks for giving them the basis for an op plan Pat!

  5. TO: dbust1;


    Only in your very small frame of reference. Everything I posted is public information and no more proprietary than the article that is the basis of this thread.

    Originally published in 2002 the following fact was republished again in 2005.

    Coke Fiend Bin Laden
    26 Jul 2005
    New York Post

    “Osama bin Laden tried to buy a massive amount of cocaine, spike it with poison and sell it in the United States, hoping to kill thousands of Americans one year after the 9/11 attacks, The Post has learned.”

    The basis of my argument. Will you now denounce the New York Post?

    Following your lead by keeping these issues under wraps is what gives our enemies their opportunity. I expose the issues to raise awareness to the deadly potential derived from continuing the war on drugs. If you are so concerned tell your representatives to end the drug war. The drug war is giving bin Laden these opportunities. The drug war gives alQaida and the Taliban this “aid and comfort”.

    I’ve been writing about these issues for years and folks like you simplistically denounce and ignore it instead of positively acting to prevent the danger by confronting your politicians.

    Drug War anarchy empowering bin Laden

  6. TO: dbust1;

    Do you actually think that bin Laden is reading the Reason Magazine ‘Hit & Run’ blog?

  7. Ron, isn’t it a little early to worry? Isn’t constructing the genome still a long way from constructing the organism?

  8. I’m glad this is a libertarian site.

    Imagine the kind of things that would be posted here if it were the typical nazi-amerikan rag.

  9. Dearest Pat,

    I happen to know for a FACT* that OBL not only reads ‘Hit & Run’ but every newspaper, blog, magazine, pamphlet & brochure w/ any mention of him, Al Qaeda, terrorism, Islam and/or spelunking that is printed in the western world. This is, of course, why the CIA cannot find him because he spends all his time researching in remote locations in Paki-Afghanistan. But seriously, I was pandering to the baser conservative elements who prefer to keep their heads firmly planted in the sand in the na?ve belief that the gov. is on top of every and any possible terror attack scenario.

    *this is an egregious lie on my part.

  10. Isn’t constructing the genome still a long way from constructing the organism?

    If it’s a virus you’re talking about, not necessarily. Many viruses can very easily and inexpensively be reconstituted if you’ve got the DNA in hand.

    DNA synthesis is way too simple to be regulated effectively. And there are probably 20,000 DNA synthesis machines outside of the U.S. anyways. There are probably better ways to address this potential threat than regulating labs in the U.S.

  11. Gene technology can bring endless benefits to the world, but also for the risk of providing an unstable time capsule.

    In particular gene synthesis technology is now increasingly low cost, lack of supervision, once the risk of irreversible global will occur. Do not forget that the global spread of the virus occurred 03 years, as long as there is a little bit out of the test product might also cause serious consequences than this event.

    The world economy has globalized, there is nothing better than this but also threatening.

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