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.

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.”

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 the bad bugs are

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.

UPDATE: More opinion at Wired Science and Danger Room.

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:

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)

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.

DNA testing is risky business for all concerned

I’ve been reading a flurry of posts and news stories over the past several days (see the latest at Wired Science) about California’s attacks on DNA testing businesses like Navigenics and 23AndMe. In what could be the opening salvo of a long and expensive battle, California’s health officials have issued cease-and-desist letters to up to 25 biotech companies that offer direct to consumer genetic testing. California says only a doctor can order a genetic test—under no other circumstances should this be available to consumers. Health Dept. official Karen Nickles made the spurious justification for this action,

“The public demand around access [to genetic information]… has created the worried well,” Nickles declared, noting that the results could be difficult for consumers to understand or act upon. “Once they get the results, they don’t know what to do about it.”

As always, the excuse is that the public is stupid and must be protected from itself. Or could it be that certain erstwhile links in the DNA chain of custody are a bit miffed about missing out on the money/data/privacy of consumers? Such as, oh, I don’t know, doctors, labs, and insurance companies who desperately want to have your genome on file? Not that they would ever use it against you—perish the thought! If you can just pay cash directly to some biotech company and get the results delivered to you, that’s a threat.

Indeed, an individual representing one of the targeted companies noted that although the health department feebly claims that its action was spurred by “multiple consumer complaints,” it’s more likely to have been spurred from within the (profit-motivated) health industry, to which I would add let’s not forget the insurance industry.

“If we could find out who put the bee in their bonnet, my guess it’s the medical community,” Greenspan [partner at DNATraits] said. “I think that the medical community doesn’t want to lose control of who orders the test.”

A couple of comments from Wired readers I thought worth repeating here….

“One (this one) wonders if insurance companies put this ‘Bee’ in the bonnet. If the individual orders the test, it does not go into the medical record, and insurance companies can not use said data to provide or deny their services. Mandating testing through medical professionals could be the first window to genetic discrimination by insurance companies…” – Matt

“Given the privacy-hostile nature of the US corporatocracy, you’d have to be crazy or incredibly stupid to hand over your genetic data to companies not bound to abide by even the token protections of HIPAA.” – realitydose

Yes, I think until a whole lot of things get figured out, I’ll stick to my policy of not handing out my DNA to anyone. Period. You’d be well advised to do the same, unless you have a very good reason to seek genetic testing at this time. If you’re just curious and have $1000 to blow, quite frankly, at this time no one can foresee what kind of risks you may be taking by enabling the collection of this data.

That’s nice, but you still can’t have my DNA

Wired Science reports that our Dear Leader signed the Genetic Information Nondiscrimination Act (GINA) law today. Theoretically, you now can’t be denied a job or insurance based on the titillating secrets hiding within your DNA. I’m sure there will be plenty of creative ways around that within 10 years or so. Further,

“GINA’s not perfect: The law doesn’t specifically keep genetic information out of third-party hands. It also doesn’t apply to the military. (So actually, you still might be denied entrance to Gattaca based on a genetic test.) And some people say health insurance won’t ever be fair without a pricing structure that makes discrimination impossible.”

The GINA law is a good thing. A great thing, even. It’s good that they can’t say, “Hmmm, looks like you’ve got a 28% chance of having clogged arteries by the age of 45, so we’re not going to insure (or hire) you.” But there is no way in hell I’m ever going to have my genome sequenced and entered into some medical record that frankly, I have zero control over. Laws change, and corruption happens. Government and businesses work out ways to do and get what they want, not to mention the fact that data of all kinds is stolen and sold on a regular basis.

I’m not trying to sell tin foil hats here, folks, but in the case of genetic data we simply do not know what the world is going to be like within 20-50 years. No, I don’t think individuals are going to be secretly “targeted” in some way but I do think genetic information will just be another way that people will be grouped and categorized, probably right out in the open, and to some end that a lot of them will be unhappy about. Since we do not yet know what we will be able to learn from or do with the genome in the future, how could we possibly know how releasing or even (supposedly) securely storing your genetic data might come back to you in the future? There could even be some sort of disadvantage to your kids who aren’t even born yet. Just a thought.

On the “open genome” side of the aisle, there are a few adventurous people so far, like Craig Venter and George Church, who are happy to have their genomes published in the name of science. Better them than me, but I guess only time will tell whether my paranoia was a waste of neurotransmitters or not.

I, for one, welcome our performance-enhanced overlords

Bioethicist John Harris writes a short op-ed here against the backdrop of the Human Fertilisation and Embryology Bill currently under debate in the UK. The bill deals with embryonic stem cell research and chimeric embryos, among other things, and apparently has people thinking we’ll be growing half-animal, half-human babies, or some such. (I’ll take the little red-headed frog baby with the six legs and the beaver tail, please.)

Harris says that eventually, enhancement technologies will bring on the replacement for the human race. And why not? If we can fix mutations that cause disease, shouldn’t we? If we can grow new eyes for a blind person or new kidneys for someone dying of kidney disease, shouldn’t we?

But people tend to start getting upset when we consider “optional” things (a purely subjective term). This is because we have a long-ingrained and useless cultural fear of playing god. The fact is, we already manipulate our bodies and our behavior every day with all manner of substances that we eat, drink, or breathe. We will soon reach a point where average people will have access to technologies—whether drugs, genes, or physical modifications of various types—that will make us question whether some of us are still human. Harris believes that our ability to modify ourselves signals the end of our familiar brand of human, at least.

While he discusses lots of benefits of our new-found technological powers, he also notes that modifications may spawn injustices (think Gattaca, or X-Men). I agree, that will definitely happen to some degree. Unless we can modify out of ourselves some of our most basic behaviors. Regardless, they can plug me in whenever they’re ready. I’m first in line for an upgrade! I’m thinking maybe wings, and definitely a neural interface for the Internets.

If this topic interests you, maybe you’ll be lucky enough to attend this session at the World Science Festival in NYC.

Update: Here’s another angle from the New Scientist editor’s blog: A human hybrid speaks out

Another $55M for biological agent countermeasures

And with my last post in mind, HHS has announced another $55M to fund countermeasures against anthrax, plague, and tularemia. From the press release:

The Department of Health and Human Services (HHS) announced today the award of contracts totaling $55.3 million to four companies for the advanced development of anthrax antitoxins, therapeutics and antibiotics for use against plague and tularemia.

The new Biological Advanced Research and Development Authority (BARDA) and NIH’s National Institute for Allergy and Infectious Diseases (NIAID), provided funding for the new contracts. Through an agreement with BARDA, NIAID will manage the contracts.

The companies receiving contracts are:

* Nanotherapeutics Inc. of Alachua, Fla. — $20 million for a plague and tularemia antibiotic development;
* Emergent BioSolutions Inc. of Rockville, Md. — $9.5 million for anthrax immune globulin development;
* PharmAthene Inc. of Annapolis, Md. — $13.9 million for anthrax antitoxin development [Note: I've posted about PharmAthene before—they're also developing recombinant human butyrylcholinesterase, or "Bioscavenger"]
* Elusys Therapeutics Inc. of Pine Brook, N.J. — $11.9 million for anthrax antitoxin development.

“These contracts will help speed the development of new interventions against anthrax, plague and tularemia, three diseases considered to be important bioterror threats,” said NIAID Director, Dr. Anthony S. Fauci. “The ‘pipeline’ of candidate bioterror countermeasures is fuller than ever, which bodes well for our ongoing efforts to protect Americans from those who would do us harm with biological weapons.”

Yes, the pipeline of candidate bioterror countermeasures is fuller than ever, because as I’ve said, that’s where the cash is. It would be reassuring to know though, that out of all this effort there are technologies and methodologies being developed that will help fight diseases that are arguably greater global health threats.

UPDATE: 8Oct07 – For another point of view on the issue, see this post at the Armchair Generalist.

“Bioterror” labs too much of a liability

As regular visitors have realized by now, I’m not currently blogging much. Too many things going on and my head’s not into blogging. But I’m still following the issues that interest me, and I might pop up here and there to share a few thoughts about them. For one, there’s this story in the New York Times: U.S. Called Lax at Policing Labs Handling Biohazards.

There’s been lots of coverage of the problems, or potential problems, with so-called bioterror or bioweapons labs since the Texas A&M lab’s operations were halted by the CDC pending investigation of biosecurity lapses. This week, as outlined in the NYT article, speakers at a hearing entitled Germs, Viruses, and Secrets: The Silent Proliferation of Bio-Laboratories in the United States discussed oversight problems with U.S. biosecurity labs, troubling growth in the BSL-3/4 lab “industry,” and associated risks. Of particular note was the testimony by Keith Rhodes of the GAO, published in this GAO report, HIGH-CONTAINMENT BIOSAFETY LABORATORIES: Preliminary Observations on the Oversight of the Proliferation of BSL-3 and BSL-4 Laboratories in the United States.

As Rhodes testified, there are now 15 BSL-4 labs in operation or planning within the U.S., but

No single federal agency, according to 12 agencies’ responses to our survey, has the mission to track the overall number of BSL-3 and BSL-4 labs in the United States. Though several agencies have a need to know, no one agency knows the number and location of these labs in the United States. Consequently, no agency is responsible for determining the risks associated with the proliferation of these labs.

The GAO report features a nice map of BSL-4 and some major BSL-3 labs across the U.S. (page 12).

As someone who works with biosecurity threat-related issues on a daily basis, the proliferation of these labs under the guise and funding of bioterrorism or biosecurity concerns me for a variety of reasons. I am not that concerned that we are training scores of new scientists to be experts in how to make the perfect weapon. I think the likelihood of “rogue” scientists perpetrating terrorist attacks is remote. Accidents are another matter. They do happen, and they will at some point, as we saw recently with the FMDV outbreak in the UK.

But my bottom line is that I don’t think we ever needed to build more of these in the first place, and certainly not in the private sector. We already have excellent biosecurity expertise and labs within the U.S. government’s public health and defense establishments, enough to provide top notch countermeasures research efforts as compared to the probability of a biological attack. The real problem is that since 9/11 and the Amerithrax attacks, we also have a massive influx of money. We direct this money towards our fear of terrorism, and of course this becomes the basis for endless proposals to get the money. It’s not about the need for the labs, it’s about the fact that there’s money, and academic & private institutions know that to get the money they’ve got to play up the fear.

Imagine if all this effort was directed toward curing cancer, HIV, or fifty other far more relevant health needs instead. And if that’s what the money was for, you can bet people would be scrambling to build labs to fill that need. Granted, these labs are fully capable of researching a number of emerging infectious diseases such as SARS and avian influenza. But the appearance is that they’re all hot to trot for juicy bugs like smallpox and anthrax. Because terrorism is king.

With that in mind, from my perspective, there’s another and even more important reason to rein in this proliferation of select agent labs: you may have noticed how the press just loves the sensationalism of calling these labs bioterror and bioweapons labs. Potential adversaries around the world notice it, you can bet on that. Would it be any surprise if the rest of the world actually believed the U.S. was creating biological weapons? This perception does serious and unnecessary damage to our own security, actually increasing the threat that other countries could feel compelled to follow suit. We need to dispel these notions for our own good.

Certainly the oversight concerns the GAO discussed need to be addressed immediately. As the GAO report concludes,

The expansion of BSL-3 and BSL-4 labs taking place in the United States is proceeding in a decentralized fashion, without specific requirements as to the number, location, activity, and ownership of such labs. While some expansion may be justified to address deficiencies in lab capacity for the development of medical countermeasures, unwarranted expansion without adequate oversight is proliferation, not expansion. Since the full extent of the expansion is not known, it is unclear how the federal government can ensure that sufficient but not superfluous capacity—that brings with it additional, unnecessary risk—is being created.

The proliferation of these labs must end. We have enough expertise, enough facilities, and more than enough funding going toward potential bioterror threats. Let’s make it clear to the world that we are going to steer the future efforts of our existing labs toward major public health threats. I am certain that much of the world would breathe a tiny sigh of relief.


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