Sarin

First let me say that I am not back from my sudden departure from the blogosphere, and I do not have an ETA for when I plan to be regularly blogging again. However, maybe as something of a tease, I do have a link to pass along to Molecule of the Day’s post on sarin.

Who among you can point out, without giving away anything you shouldn’t, what’s wrong with the post?

Spertzel: wrong on weaponized anthrax

So Richard Spertzel, former U.N. weapons inspector, had this to say in WSJ:

Information released by the FBI over the past seven years indicates a product of exceptional quality. The product contained essentially pure spores. The particle size was 1.5 to 3 microns in diameter. There are several methods used to produce anthrax that small. But most of them require milling the spores to a size small enough that it can be inhaled into the lower reaches of the lungs. In this case, however, the anthrax spores were not milled.

What’s more, they were also tailored to make them potentially more dangerous. According to a FBI news release from November 2001, the particles were coated by a “product not seen previously to be used in this fashion before.” Apparently, the spores were coated with a polyglass which tightly bound hydrophilic silica to each particle. That’s what was briefed (according to one of my former weapons inspectors at the United Nations Special Commission) by the FBI to the German Foreign Ministry at the time.

Another FBI leak indicated that each particle was given a weak electric charge, thereby causing the particles to repel each other at the molecular level. This made it easier for the spores to float in the air, and increased their retention in the lungs.

Um, no.  I’ll trust a peer-reviewed assessment over some policy-pressurized briefing, thank you.

According to the FBI scientist who analyzed the anthrax letters, Douglas Beecher, it was NOT “weaponized.” He published this in Applied and Environmental Microbiology in 2006.

Individuals familiar with the compositions of the powders in the letters have indicated that they were comprised simply of spores purified to different extents (6). However, a widely circulated misconception is that the spores were produced using additives and sophisticated engineering supposedly akin to military weapon production. This idea is usually the basis for implying that the powders were inordinately dangerous compared to spores alone (3, 6, 12; J. Kelly, Washington Times, 21 October 2003; G. Gugliotta and G. Matsumoto, The Washington Post, 28 October 2002). The persistent credence given to this impression fosters erroneous preconceptions, which may misguide research and preparedness efforts and generally detract from the magnitude of hazards posed by simple spore preparations.

Purification of spores may exacerbate their dissemination to some extent by removing adhesive contaminants and maximizing the spore concentration. However, even in a crude state, dried microbial agents have long been considered especially hazardous. Experiments mimicking laboratory accidents have demonstrated that simply breaking vials of lyophilized bacterial cultures creates concentrated and persistent aerosols (4, 8). The potential for propagating disease with crude lyophilized material is illustrated by an outbreak of 24 cases of Venezuelan equine encephalitis throughout three floors of a Moscow virology institute. These infections were caused when vials containing dried infected mouse brain were accidentally broken on a stairwell landing and were spread by air currents and foot traffic (11).

Can we just put this to rest? Dry it, grind it up. It’s good enough for envelope dissemination. Poof!

So begins the hand-wringing about mad biodefense scientists

As I mentioned in my two previous posts about the Amerithrax suspect, (here and here), the entire country will soon be all tits-a-flutter about the looming threat of mad biodefense scientists.

Science magazine joins in with this article and soundbites from Gerald Epstein and Jonathan Tucker.

Biodefense researchers were pondering today whether there might be a backlash to their field if the worst bioterror crime in U.S. history was indeed committed by a scientist who had spent a career developing countermeasures against anthrax. But the fact that Ivins won’t face trial also raised the uncomfortable specter that the full truth about the case may never come out. “We may never know for sure whether he did it or not,” says virologist Thomas Geisbert, a former USAMRIID researcher now at Boston University.

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The death–and presumed involvement in the anthrax letters–puts the biodefense research community in a tight spot, says Gerald Epstein, a biosecurity expert at the Center for Strategic and International Studies in Washington, D.C. “From the very beginning, there has been speculation that the attacks were carried out by a biodefense zealot who wanted to prove that bioterrorism was a serious problem,” says Epstein. If true, that could give the public the impression that “biodefense research is a giant fraud,” he says. “It would be unfortunate if the message people take away from this is that the only individuals we should be concerned about are deranged biodefense scientists.”

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Jonathan Tucker, a specialist on biological weapons control, says the incident is bound to evoke new concerns about “insider threats” at government and university labs. Officials may be compelled to further scrutinize researchers who work with select agents, Tucker says, adding that some questions have already been raised about “the adequacy of the screening process” used by the FBI to determine if a scientist should be allowed to work with a dangerous pathogen.

Where bad bugs are

This issue has been debated for a long time. Several years ago I would have pooh-poohed the idea that highly trained and vetted scientists would present such a risk.  But for at least the last couple of years I’ve felt that the expansion of biodefense labs is related not to research need but to homeland defense money.  If you build it they will come, and a couple of them might be frakking nuts.  Do we not now have enough investment in the study of the most dangerous, but least likely threats? How much more likely do these threats become, due to expanding the numbers of labs people handling them?

On the other hand, if Ivins was our guy, he’s been working in biodefense for nearly 20 years. Who knows when he could have gone over the edge? Would anyone have known? His coworkers seem to have liked him and don’t believe he was responsible, by the statements we’ve seen so far.

It may be that the risk of a deranged scientist is one that we’ve already taken all possible precautions against.  Screenings, protocols, security policies, all of these are already in place. There’s been some discussion of inculcating a “life scientist’s code of ethics” at universities—a noble initiative but will have zero effect on someone who is already there intending to become an insider threat.

I don’t know the answer, but I know that you’re going to be seeing a lot of this hand-wringing in the days and weeks to come.

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UPDATE: More opinion at Wired Science and Danger Room.

Nature says social scientists + DoD = win-win

Thanks to the tip from the Zero Intelligence Agents blog, I followed Drew Conway’s emphatic instruction to “Go read this right now!“  And was surprised to see Nature editors encouraging social scientists to embrace the military’s human terrain teams. The Nature editors have concluded that despite the obvious potential for abuse,

Social scientists…should embrace the opportunities that the AAA pointed out last November in a report on engagement with the military. These include studying military and intelligence organizations from the inside and educating the military about other cultures and societies.

I agree. Having been almost swayed by the softer science of cultural anthropology years ago in college, and remaining an amateur student of human behavior (often my own), I have to say: Hey social scientists, what’s the downside (uh, besides a somewhat greater chance of being shot than living in D.C.) of having this incredible opportunity for field study of not Iraqis or Afghanis, but the U.S. military.  The military is full of cultural oddities, and it’s a regular smorgasbord of social pathologies.  Many of them necessary, some not so much.

The whole idea is entirely progressive for the military (did I just use that word on my blog?).  Of course, Nature didn’t pass up the opportunity to backhand the Bush administration for its crappy record on science. But it gave the military a break on this, which seems like a decent olive branch to me.  It’s time for those social scientists who have been criticizing the program to take another look at reality.  It is what it is, not what you wish it was.  Do your jobs and study it.

Contribute to the discussion on synthetic biology

Last week I mentioned a newly published paper on the creation of artificial DNA. There are also lots of efforts out there working on synthetic lifeforms and the development of a mix & match catalog of parts for them. How far should synthetic biology go, and what kinds of benefits do you think humans will realize from it? Who should be overseeing and regulating the field? Advancements in synthetic biology may (arguably have) outpace the answers to these questions.

Dr. Gregor Wolbring at the University of Calgary is the convener of a team of four undergraduate students that looks into the ethical, legal, social issues of synthetic biology. The “Calgary iGEM Ethics Team” will present their finding at the International Genetically Engineered Machine Competition iGEM.

The Calgary iGEM Ethics team is the first undergraduate team allowed to look into the ethical, legal, social issues of synthetic biology. The students developed this survey and plan to use this survey as one output for its November presentation.

The purpose of this study is to better understand the level of knowledge you and others have about the emerging field of synthetic biology, what you feel the future of synthetic biology holds, what you feel the implications of advances in synthetic biology may be and what you think the framework of governance for synthetic biology should be.

One definition of synthetic biology is: the design and construction of new biological parts, devices, and systems: and the re-design of existing, natural biological systems for useful purposes.

You will be asked a series of questions regarding to the emerging scientific field of synthetic biology, its future, and its governance. You will have to answer 41 questions of the online survey.

You find the survey here: https://www.surveymonkey.com/s.aspx?sm=u3DnQ2vRzuA2RF_2bMb8KYaw_3d_3d

The International Genetically Engineered Machine Competition is the premiere Synthetic Biology competition and currently the largest Synthetic Biology conference in the world. Working at their own schools over the summer, participants use standard biological parts to design, build, and operate biological systems in living cells. During the first weekend of November, they share their work at the iGEM Competition Jamboree at MIT and in competition for a variety of awards for excellence.

They add their new parts to the Registry of Standard Biological Parts for the students in the next year’s competition.

Please pass this information on through your networks so that the students get many responses to the synthetic biology survey they designed. They worked very hard on the survey.

Source: Dr. Wolbring

The survey is long and parts of it could be more clear in my opinion, but if you have an interest in synthetic biology I encourage you to take it.

(via NanoWerk)

A new kind of Frankenfood: the tomato vaccine

Korean scientists have performed some promising tests using GM tomatoes that grow their own edible vaccines. In this case, against Alzheimer’s disease. And why not – the idea’s not a new one (although this guy notes a rather important reason why edible vaccines would be “a disaster” – each tomato would produce a variable level of the vaccine).

We already eat specific foods precisely for their purported health benefits. We’ve created other foods that produce desired substances, for example, the golden rice that produces large quantities of beta-carotene.

Still, something about it makes me leery. Kind of like “meatri” – synthetic meat. I’d know it was real meat, grown by the same biochemical mechanisms that animals use to grow their own meat. But I’d feel kind of hesitant to eat it, at least the first time. There’s a yuck factor.

From my own perspective of course, I also wonder how might this be used as a threat. A vehicle for biowarfare? Well, I imagine there are all kinds of toxins and such that food could be engineered to express. But there would be no reason to go to all that trouble when there are far more productive, established methods to crank out and deliver weapons. So this will no doubt remain in the realm of sci-fi for the foreseeable future. Could make for a great short story, though.

Artificial DNA

Hot off the press:

Chemists in Japan report development of the world’s first DNA molecule made almost entirely of artificial parts. The finding could lead to improvements in gene therapy, futuristic nano-sized computers, and other high-tech advances, they say.

Here’s the full text at The Journal of the American Chemical Society. Update: sorry – forgot to mention you need a subscription for that link.

Interesting new vaccine production method

There’s a lot of innovative work being done to develop new ways to jumpstart our immune systems, both in the “immune system trigger” part, and the packaging. For instance, there are efforts focused on virus-like particles (VLPs), liposomes, and various nano-structures (a couple of examples). This week in Science, a team including Eckard Wimmer, famous for de novo synthesis of poliovirus, reports its work in exploiting “codon pair bias” to create weakened poliovirus strains with great vaccine potential. Science mentions two teams currently exploring this method—Wimmer’s at Stony Brook University, and a team led by Olen Kew at the CDC.

We currently have a live poliovirus vaccine that is not without risk of causing the illness it is supposed to prevent. The thinking on this new strategy is that the genetically crippled virus could never mutate in such a way to overcome all of its flaws; further, the methodology could possibly be applied to any virus to create new vaccines.

Here’s the abstract:

Virus Attenuation by Genome-Scale Changes in Codon Pair Bias

J. Robert Coleman,1 Dimitris Papamichail,2* Steven Skiena,2 Bruce Futcher,1 Eckard Wimmer,1† Steffen Mueller1

As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific “codon pair bias” provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over- or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid–independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This “death by a thousand cuts” strategy could be generally applicable to attenuating many
kinds of viruses.

Because everyone wants to coin a catchy phrase I guess, they call the method “synthetically attenuated virus engineering” or SAVE. The paper sums the potential benefits:

…these results suggest that synthetic attenuated virus engineering (SAVE) could play a role in creating new vaccines for various types of viruses. By deoptimizing codon pair bias, one could systematically attenuate a virus to variable but controllable and predictable extents. This approach has four key features: (i) It produces a virus encoding precisely the same amino acid sequences as the wild-type virus, and therefore eliciting the same immune response. (ii) It is a systematic method apparently applicable to many viruses, and possibly not requiring detailed, virusspecific research. (iii) The attenuation is not subject to reversion, simply because of the sheer number of mutations. (iv) It can be combined with other attenuating changes (such as amino acid changes from adaptation of the virus to low temperatures or alternative species) or with other synthetic biology approaches to attenuation (18, 19), thus taking advantage of additional modes of attenuation while providing the unique advantage of limited reversion.

Codon pair bias is a little more complicated twist on codon usage bias (or just codon bias) which is a principle that has been applied in codon optimization for synthetic genes. Greatly simplified, in the genome there are multiple three-letter codons that can result in single amino acids, but some just seem to translate better than others. This preference can be used to promote high levels of gene expression in a selected organism, for instance. If you do the opposite, though, you can produce an organism that the body recognizes as a threat, but it really isn’t because it just can’t quite get the job done. It’s like an instruction manual written in Engrish. You know it’s an instruction manual but damned if you can understand it.

Here’s another writeup at ArsTechnica.