Biological Agents Risk Assessment: Fill & Download for Free

This answer may contain sensitive images. Click on an image to unblur it.Hmm, even if they aren’t hard to acquire (which I doubt as getting these infectious bio-agents entail a high degree of processing/development for use), a lot of critical issues might arise.This is because such terrorist or crazy fellow needs to take serious precautionary measures (safety precautions) in line with risk assessment and biological containment (so as not to fall victim too). The person/organization also stands the chance of facing grave sanctions (if caught) for violating the Geneva Protocol on the prohibited use of biological weapons.And as for the usage, well, bio-weapons have been used in history especially in times of war (and some might still be currently engineered for future *unlawful* deployment - who knows?).Image Credit: WikiwandNotable examples include Bacillus anthracis (anthrax), Clostridium botulinum (botulism), Variola major (small pox), Francisella tularensis (tularemia), Yesinia pestis (plague), as well as Marburg and Ebola viruses. There’s also an established use of aflatoxins (from Aspergillus flavus) as biological weapons. The trichothecene mycotoxin (T-2) produced by Fusarium tricinctum also presents another interesting case (alimentary toxic aleukia [ATA] and the Yellow Rain incident).

The question needs a little bit of definition.If it’s going for full-throttle – ie, that the U.S. government released fully weaponized biological agents over large population centers – then the answer is, “No.” Risking the destruction of Chicago with anthrax would be counterproductive to keeping a secret weapon, well, secret (although such a brazen act against the populace could have served as a massive psychological weapon against the Soviets).But if we scale the question back to the limited release of supposedly “harmless” or benign pathogens that could be a component (or facsimile) of a bioweapon, and we make a point to consider military personnel as citizens, then yeah, the government has done that.Most of these tests took place under the-not-at-all ominously-named Project 112, which began in the 1960s and continued until 1974 to gauge the U.S.’ vulnerability to biological and chemical attacks. The tests conducted under Project 112’s auspices were largely done without test subjects’ consent or awareness – such as the release of biological agents and simulants at major Washington, DC, transportation hubs and the New York City subway, and the targeting of livestock in rural states.Another major component of Project 112 was Project SHAD – an operation designed to assess the vulnerabilities of ships to bioweapons and to develop decontamination procedures. Ships were towed just off the coast and then sprayed with various agents and simulants – with crews supposedly shielded, although anecdotal evidence suggests that wasn’t always the case, or that the protection was functionally insufficient.In testimony before Congress in 2002, the Department of Defense summarized the risk to service members:In those instances when potentially harmful substances were used, there is no evidence that any of the service members involved were exposed to them without proper protection. Service members were vaccinated before testing that involved live biological agents. If actual chemical agents were used they were confined to airtight sections of their ship. When appropriate, protective clothing was also worn. While some service members may not have known all the details of these tests, it is likely they knew that they were participating in testing due to use of precautionary measures. We have learned that the scientists involved informed senior leaders about tests using simulants. Like other operational activities, service members were not informed of these tests.While initially intended to test the U.S.’ vulnerability to biological and chemical warfare, Project 112 and similar programs expanded to develop the U.S.’ biochemical offensive capabilities by repeatedly testing dispersal techniques (to include mosquitos). These programs hit their zenith in the late-1960s, until President Nixon disavowed biological warfare and committed to dismantling the U.S.’ capabilities (made effective with the Biological Weapons Convention, ratified the year after Project 112/SHAD officially ended with the closing of the Deseret Test Center).So while - strictly speaking - these tests were not conducted to test the potency of any particular bioweapon, the military's assessment of the viability of dispersal vectors had a very human element.The existence of Project 112 was kept secret for almost 30 years, until investigative journalists broke the story in 2000. In 2002, Congress directed the declassification of Project 112 materials in order to identify servicemembers who may have been affected so that they could receive VA benefits, and subsequently required VA to sponsor studies by the Institute of Medicine into possible long-term consequences of testing.Somewhere around 6,000 personnel have been identified as having been possibly exposed (mostly via Project SHAD). Although IOM found no conclusive evidence that exposure to these tests resulted in a higher prevalence of diseases than among non-participating veterans, Project 112/SHAD veterans are included in a specific priority status among VA’s enrolled health population along with other veterans who may have been exposed to environmental contaminants.At the same time as Project 112, the military was running Operation Whitecoat, in which several thousand volunteers (mostly conscientious objectors) allowed themselves to be injected with various biological agents that could be weaponized in order to test their effective dose levels. But whereas Project 112 participants had a mix of informed consent and follow-up treatment, Whitecoat participants were better monitors and treated for their exposures - although only over the short-term. Possible long-term consequences to the participants are not as well studied.

Although this might seem like a laughable goal, several research institutes are involved with computational biology to achieve a working model of human development or human tissue function. As one can imagine, such a model would be incredibly valuable for determining what stages of development are particularly sensitive to chemical exposure, or to determine how genetic manipulations or mutations would impact tissue or organ function, or to determine if a pharmacological therapy would be efficacious in a particular person, or could help answer lingering questions in developmental biology about the impact of genes and gene networks on developmental processes, etc. Cells are incredibly complex, but since they follow the laws of physics, it is theoretically possible to model a cell using known mathematical and computational models for mechanics (mechanotransduction), biochemistry, mass transport, and other fundamental phenomena for which mathematical models exist. However, given the shear number of functional genes in the human genome (a minimalist bacteria needs only 473 genes to survive[1][1][1][1]and reproduce , but human cells need much more to organize into multicellular tissues and organs), it is taxing and difficult to generate models of something as fundamental as the human cell, though such models exist for model unicellular organisms (see the figure below).[2][2][2][2] Computational biologists have gotten fairly good at designing computational models of biochemical interactions, cell functions, and agent-based models for tissues and particular biological phenomena, but the tricky part will be integrating all of these models into a single working model that is complex enough to be instructive but simple enough to run on available computers.Figure: Computational model for mycoplasma. [3][3][3][3] Based on this figure, one can appreciate the complexity involved in setting initial conditions and analyzing even a limited subset of cellular processes necessary for life. For human cells, additional biological processes like tension development, migration, multicellular organization, etc would need to be built into the model for it to be instructive towards a more comprehensive model of a human.The model you’re discussing is the ultimate goal of the project I’m currently working on for the EPA, which is a continuation of an effort that started several years ago called the Virtual Embryo Project. The goal from the EPA’s perspective is to use systems biology to build and validate models of developmental processes that could be useful for screening applications.[4][4][4][4] The EPA has a suite of assays to determine putative modes of action (molecular initiating events) for toxicants (ToxCast, Tox21),[5][5][5][5] and one of the goals of the Virtual Embryo Project (now called the Virtual Tissue Models projection) is to build these molecular perturbations into in silico model that could help inform risk assessment through predictive and computational toxicology. I don’t expect all of the words in this paragraph to make sense to you, but basically, what you proposed in your answer is a real possibility and would be greatly valuable to folks in toxicity assessment, pharmaceuticals, and life science/ecology in general.I won’t give a definite answer of ‘when’ a molecular computational model of a human would be possible, but I believe that a working model could be achievable within my lifetime.Footnotes[1] Design and synthesis of a minimal bacterial genome[1] Design and synthesis of a minimal bacterial genome[1] Design and synthesis of a minimal bacterial genome[1] Design and synthesis of a minimal bacterial genome[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413483/[4] Virtual Tissue Models: Predicting How Chemicals Impact Development[4] Virtual Tissue Models: Predicting How Chemicals Impact Development[4] Virtual Tissue Models: Predicting How Chemicals Impact Development[4] Virtual Tissue Models: Predicting How Chemicals Impact Development[5] Toxicity ForeCaster (ToxCast™) Data[5] Toxicity ForeCaster (ToxCast™) Data[5] Toxicity ForeCaster (ToxCast™) Data[5] Toxicity ForeCaster (ToxCast™) Data