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Synthetic Genetic Shakespeares

Examining the implications of science and technology

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Synthetic Genetic Shakespeares

The personal blog of Tyler Kokjohn. A partial list of my scientific publications may be found on PubMed. I declare no competing scientific or financial interests regarding the topics examined in this blog. All rights reserved.

Can We Save the Bighorn Sheep?

Game managers charged with expanding bighorn sheep (Ovis canadensis) populations must perform a delicate balancing act (1).  All they have to do is find suitable habitat that is not too close to domestic sheep which may transmit diseases to bighorn, but not so remote that hunters can’t get at them.  Those have been vexing problems, but it turns out that efforts to establish new herds or bolstering numbers of existing populations by transplanting in new sheep has another complication.  The transplanted animals themselves might be reservoirs of diseases that could threaten the health and survival of the herd (1).

Bighorn

Bighorn sheep populations are believed to have once numbered in the millions and extend over wide regions of North America.  Incompatible with human settlement, the species had declined almost to the point of extinction by the start of the twentieth century (2).  Establishment of national parks, wildlife refuges and active conservation efforts have enabled some recovery, although only to levels of probably less than 1% of the pre-settlement era (2).

Because small herds are at greater risk of inbreeding and dying out from predation or other factors, managers would like to supplement their numbers by transplantation.  Now they have recognized that activity brings with it some risk of transplanting potentially deadly disease agents as well (1).  Damned if they do and damned if they don’t, managers are caught in a bind trying to figure out how to keep small, isolated bighorn herds viable over the long term.       

The bighorn sheep transplant story reminds me of reports of a human disease condition known informally as “stranger’s cough” or “boat cough” (3).  Geographic isolation may have set up a situation where persons inhabiting the remote Scots archipelago of St. Kilda seem to have become more susceptible to respiratory diseases that were comparatively mild in persons from the mainland.  Living in physical isolation inadvertently kept them away from a lot of respiratory bugs that were commonly passed from person-to-person in heavily populated locations.  That lack of routine exposure set the islanders up to have nasty epidemics when travelers from afar brought in forms of disease agents they had not encountered.  A retrospective analysis suggests that the most probable etiologic agent for the severe condition termed stranger’s cough was rhinovirus, the cause of the usually rather benign common cold (3).

Drawing from the stranger’s cough story we can see some parallels to the problems facing bighorn managers in Montana and other locations today.  Some of the descriptions in a recent news article (1) fit the basic St. Kilda model in which new arrivals carry a risk to transmit disease to the rest of the herd.  In addition, the observations that wild sheep now harbor quite a few pathogens and could be “infecting themselves” coupled with the fact that large herds near Yellowstone carry pathogens, but do not have mass die-offs (1) fit in as well.  Taken as a whole, the information suggests the bighorn problem is directly analogous to the plight of the isolated islanders (3) with epidemics touched off by the arrival of a novel strain of “M. ovi” (1). 

The article (1) does not explicitly state that “M. ovi” is Mycoplasma ovipneumoniae, but this pathogen is known to cause disease in domestic and wild sheep.  It certainly is a good place for veterinarians seeking the bighorn disease outbreaks culprit to start.  However, they may have a hard time figuring out which agent(s) to blame.  What is actually killing bighorn after transplant actions may not necessarily be the same microbes that typically create problems in wild and domestic animals.  M. ovipneumoniae is known to promote secondary infection by viruses or bacteria that finally kill their weakened hosts. Worse, deaths may not necessarily be due to the same agent every time in the different herds.  Each bighorn subpopulation existing in fragmented pockets of suitable habitat may succumb to something different due to sheer happenstance.  This is a complicated situation, one that may be hard to control with antibiotics or vaccines. 

Looking at the numbers, it is clear the vestigial bighorn sheep population has been on the verge of complete extinction for over a century.  This difficult – and dangerous – situation makes careful and systematic examinations of animal transplant practices and outcomes essential.  At this stage it is hard to decide when reintroduction efforts have succeeded (4) or whether they are now even advisable.  Bighorn sheep once roamed the west in numbers thousands of times greater than today.  They were important enough to the peoples of ancient times that quite a number of petroglyphs were created that seem to depict them (2).  May the game managers of our time find a way to preserve this species. 

Petro2

 

Special thank you to Cyndi Tuell, Arizona wildlife expert and advocate for pointing out the article by Laura Lundquist.

(1) Laura Lundquist.   Montana FWP Backs Away From Plans to Establish New Bighorn Sheep Herds.  Missoula Current, 15 November 2018.  https://www.missoulacurrent.com/outdoors/2018/11/montana-bighorn-sheep/

(2) The National Wildlife Federation. Bighorn Sheep.  https://www.nwf.org/Educational-Resources/Wildlife-Guide/Mammals/Bighorn-Sheep

(3) P. Stride. 2008.  The St. Kilda Boat Cough Under the Microscope.  Journal of the Royal College of Physicians of Edinburgh 38:272-279. https://www.rcpe.ac.uk/college/journal/st-kilda-boat-cough-under-microscope

(4) Doug Kreutz. Bighorn Reintroduction Near Tucson Could Soon be Declared a Success.  Arizona Daily Star, 1 September 2016.  https://tucson.com/entertainment/outdoors/hiking/bighorn-reintroduction-near-tucson-could-soon-be-declared-a-success/article_aba02910-5e8f-5d35-bb0e-fef79a25e872.html

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The Most Dangerous Virus of All

As we passed the 100th anniversary of the killer influenza pandemic, former White House Ebola Response Coordinator, Ron Klain, reminded us that despite a century of medical advances the chances of infectious disease disaster are increasing (1).  To prevent future calamities, he urges the medical community to expand its public health protection efforts beyond the traditional focus on research and reaction to epidemics after they appear.

The Aftermath of Globalization

Efficient and convenient transportation systems have encouraged the expansion of globalized trade and tourism.  Human and animal pathogens have traveled with us or our products for centuries, sometimes changing the course of human history along the way (2).  However, the fact that infectious disease agents often move as fast as we do means we are now enabling the world-wide spread of a more diverse array of pathogens at unprecedented velocities.  Consider the 2014 Ebola epidemic.  Courtesy of air travel, in a matter of hours this deadly virus soared from Africa to Dallas, Texas, where it caught Emergency Department medical professionals off guard (3).

Rancor in the Ranks

The current contentious political climate in the U.S. may impact infectious disease control efforts.  The classic problem faced by public health authorities is that much of their success is often so invisible.  Legislators under pressure to fund a physically concrete and politically symbolic border wall have proposed cutting proactive international programs from the National Institutes of Health and Centers for Disease Control and Prevention.  While there is a constituency advocating loudly for a wall, few herald the quiet efforts that likely help prevent epidemic disease outbreaks. 

Can’t we just seal ourselves off and halt infectious diseases before they cross the borders?  That strategy is destined to fail regularly because some diseases are undetectable during the incubation period.  For example, pre-boarding screening procedures failed – twice – to identify the first U.S.-bound commercial air traveler unknowingly incubating Ebola virus (3).  In addition, we now must take account of the fact that our living situations are changing in ways that expand the threat of disease epidemics.  Human populations are increasing and more people are concentrating in large cities.  Many diseases emerge from wildlife (4) and as humans spread over an ever-greater share of the living space on planet Earth, the chances for contact with reservoir animals with subsequent infectious agent transmission increase.  These currently unstoppable trends coupled with climate change, mass migration along with fast air and sea transportation systems (2, 4) place us in a self-catalyzing vicious circle of increasing risk from emerging diseases for the foreseeable future.

Mr. Klain and others (5) have noted that health professionals now face a particularly challenging environment of public skepticism regarding vaccine use and safety.  Social media and the information preference bubbles (6) they may foster have provided fertile grounds to amplify misinformation and outright disinformation seeded by sincere individuals as well as other actors (7) advancing destructive agenda.  Mr. Klain urges the medical community professionals to expand their efforts in new, probably unfamiliar realms by joining public conversations including those taking place on social media.  The Vaccine Confidence Project (5) is taking proactive action to keep abreast of worrisome developments and counter them, but more members of the medical community will need to get engaged to quell the tide of illegitimate information.           

The Most Dangerous Virus of All

The 1918 influenza pandemic caused immense loss of life and suffering.  Physicians of the 21st Century understand the etiologic agent and possess the means to control and sometimes prevent disease caused by flu viruses.  Unfortunately, the advances in medicine accrued over the last 100 years may be negated by a newly emerged, potentially disastrous threat to public health – unreliable information propagated en masse on social media that overwhelms expert advice (5).  Facebook, Twitter and other social media venues will clearly be the high-stakes opinion battlefields of our future.  Unless the medical community wakes up to the threat, a single, fallacious post in the digital world that goes viral might exact a terrible toll.      

Danger 3

(1) Ron Klain.   Politics and Pandemics.  The New England Journal of Medicine, 7 November 2018.   https://www.nejm.org/doi/pdf/10.1056/NEJMp1813905

(2) Susan Brink.   Yellow Fever Timeline: The History of a Long Misunderstood Disease.  NPR, 28 August 2016.  https://www.npr.org/sections/goatsandsoda/2016/08/28/491471697/yellow-fever-timeline-the-history-of-a-long-misunderstood-disease

(3) Greg Botelho and Jacque Wilson.   Thomas Eric Duncan: First Ebola Death in U.S.  CNN, 8 October 2014.   https://www.cnn.com/2014/10/08/health/thomas-eric-duncan-ebola/index.html

(4) A. A. Cunningham et al. 2017.  One Health, Emerging Infectious Diseases and Wildlife: Two Decades of Progress? Philosophical Transactions of the Royal Society B 372:20160167.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468692/

(5) Heidi J. Larson.   The Biggest Pandemic Risk?  Viral Misinformation.  Nature, 16 October 2018.  https://www.nature.com/articles/d41586-018-07034-4

(6) Clint Watts.   Messing with the Enemy, HarperCollins.

(7) Jessica Glenza.   Russian Trolls ‘Spreading Discord” Over Vaccine Safety Online.  The Guardian, 23 August 2018.  https://www.theguardian.com/society/2018/aug/23/russian-trolls-spread-vaccine-misinformation-on-twitter

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It’s Alive! Digital Frankensteins Discover Evolution

Visionary computer programmers have created several spectacularly successful and world-changing social communications systems.  However, the passage of time has revealed that even visionaries have limits (1, 2).  It is clear that these talented and driven persons did not foresee some unsettling ramifications of their inventions until after damage had been done.         

Frank Castle 2

The Evolution of Facebook

Reminiscent of the fictional creature patched together by Victor Frankenstein, this new in silico entity engaged in activities unforeseen by its programmer-architects.  Frankenstein’s abandoned wretch acquired language and knowledge of the world by stealthily observing others.  The tabula rasa total surveillance system we know as Facebook likewise learned by observation to ultimately become both a seductive mirror and manipulator of its human users. The sophisticated data harvesting operation and advertising intermediary of today bears scant resemblance to the original corporate concept.  

A Frontline documentary (1) traces the history of Facebook from inception to monopolistic communications facilitator behemoth.  Much of the story is conveyed in the words of Mark Zuckerberg and it is fascinating to see how his assertions of what Facebook was doing changed over time.  As the engineers worked industriously to make the site interesting and devised ways to monetize a prodigious harvest of data, you may find yourself wondering when these people realized they no longer fully controlled all the real world consequences generated by their complex creation.  The unfortunate answer is that unwelcome revelation seems to have only come years after several clear and direct danger warnings had been issued.               

Move Fast and Break Things

Facebook leaders reasonably should have known there was potential to employ social media content to manipulate the public because the company has been involved in research to investigate such things (3, 4, 5).  However, when it came to reacting to the use of its systems to influence elections, foment unrest or enable systematic violence, the Facebook motto – move fast and break things – was forgotten.  After a period of blanket denials, the corporate leaders interviewed by Frontline repeated the same narrative; we reacted to the situation too slowly.  Now that they admit to oversights and shortcomings, will they live up to repeated promises to manage situations better?  We are still left wondering if a company so clearly behind the curve on serious consequential impacts and damages from their technology can ever hope to catch up to fast-evolving events.  The fact that Facebook is now a global business serving billions of customers immediately signals the immense complexity associated with efforts to assess, interpret and control activities as necessary.  A global business activity footprint imposes new responsibilities on leaders, but CEO Zuckerberg would clearly prefer to evade these duties (6). Once again, this seems to be shaping up to be another instance where Facebook reluctantly reacts to unwelcome realities.            

There’s an App for That!

The unwritten canon of technology firms is that the answer to every question is technology or more technology.  Social media are causing concern that these communications tools too often end up impairing information exchange.   Is there a means to ensure people getting news feeds through social media services that have been catered carefully to their particular tastes do not become lodged in restrictive preference bubbles?  For anyone determined to broaden their perspectives on the news several apps are available (7, 8).  How many consumers will embrace and use such apps is unclear. 

Whether effective coding solutions to combat the information bubble impoverishment phenomenon, fake news, unethical third-party data harvesters and discord-enhancing trolls can be created remains to be seen.  Facebook along with other communications networks are evolving in directions both deliberate and unanticipated.  The digital instantiations of the Red Queen (9) should be appearing shortly.

(1) Frontline.  2018.  The Facebook Dilemma. https://www.pbs.org/wgbh/frontline/film/facebook-dilemma/

(2) David Streitfeld.   2018.  Where Trolls Reigned Free: A New History of Reddit. The New York Times, 30 October 2018.    https://www.nytimes.com/2018/10/30/books/review/christine-lagorio-chafkin-we-are-the-nerds.html

(3) Ben Quinn and James Ball.   2014.  US Military Studied How to Influence Twitter Users in Darpa-funded Research.  The Guardian, 8 July 2014.  https://www.theguardian.com/world/2014/jul/08/darpa-social-networks-research-twitter-influence-studies

(4) Dominic Rushe.   Facebook Sorry – Almost – For Secret Psychological Experiment on Users.  The Guardian, 2 October 2014.  https://www.theguardian.com/technology/2014/oct/02/facebook-sorry-secret-psychological-experiment-users

(5) Euan McKirdy.   2018.  Facebook: We Didn’t Do Enough to Prevent Myanmar Violence.  CNN, 6 November 2018.  cnn.it/2DnKHgF

(6) Alex Hern.   2018.  Pressure Grows on Zuckerberg to Attend Facebook Committee Hearing.  The Guardian, 7 November 2018.  trib.al/O0geU4v

(7) Shaunacy Ferro.   2017.  This App Helps You Read a More Diverse Range of Political News.  Mental Floss, 15 March 2017.   http://mentalfloss.com/article/93288/app-helps-you-read-more-diverse-range-political-news

(8) Chris Velazco.  2018.  Google’s News App is a Toll for Gaining Perspective, Not an Arbiter of Facts.  Engadget, 11 May 2018. https://www.engadget.com/2018/05/11/google-news-app-perspectives/

(9) The Red Queen Hypothesis.  https://en.wikipedia.org/wiki/Red_Queen_hypothesis

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War of the World Views – When Blowhards Fan the Flames of Fear

One day prior to the 80th anniversary of the legendary ‘The War of the Worlds’ radio broadcast (1) we may have caught a glimpse of the frightening future of news coverage.  I first noticed an eye-catching story in my Twitter feed when journalist Carl Zimmer (@carlzimmer) debunked part of it.  His particular concern emerged from a broadcast/cable news program when a featured guest asserted immigrants could bring smallpox into the United States.  Thanks to sustained vaccination programs, natural smallpox transmission has not been seen anywhere on Earth for over 40 years (2).  For all practical purposes smallpox is extinct and there is no reasonable possibility anyone in the migrant caravan now inching toward the United States will be carrying this disease along with them.

Misinformation Refuted Fast and Easy        

This erroneous smallpox scare was easy to discredit and from the Twitter timeline it appears that Carl Zimmer (and others) responded within minutes to the posting of that story.  Although a swift social media response squelched the smallpox threat misinformation almost as soon as it appeared, it is unknown if everyone who heard or saw the original smallpox scare story also got (and accepted) the knowledge antidote.

Lessons of ‘The War of the Worlds’ 1938 Broadcast      

The New York Times article (1) commemorating Orson Welles’s retelling of a dramatic story on radio reminds us that broadcast never produced the massive public hysteria an entrenched mythology would have us believe.  However, the events of 1938 provide some guideposts about how people react to frightening news stories.  That radio broadcast reached a sizeable audience pre-primed by then-unfolding political events to be concerned about foreign invasion.  Stories presented in the media may not always alter preconceived notions of an audience, but they so seem to readily fortify preexisting beliefs.  And when persons share news it becomes even more compelling. 

Take a moment to consider what you believed about the public reaction to Orson Welles’s broadcast before having read the NYT article.  Was your personal narrative truth, myth or a bit of both?  Perhaps another important lesson for us today is that a compelling story can become persistent and broadly accepted canon in spite of the facts. 

The Big Picture – You Are Now the Target and the Mechanism

Social media now provide a universe of opportunities to amplify eye-catching news sharing to extraordinary extremes.  This isn’t your grandfather’s propaganda; portions of the social media worlds have been transformed into active, potentially disorienting and uniquely hostile information exchange environments.  Persons, organizations and even bot impersonation programs have all attempted to amplify political antagonisms and fan the flames of social strife wherever it was found (3-5). 

Clint Watts (7) offers a bleak assessment as to where some current trends are taking us –           

Fake news is a fuel used by social media manipulators to power preference bubbles that will ultimately create serious dangers for all of society.  Today’s preference bubbles, which abhor compromise and debate, will use manufactured falsehoods not only to confirm their preferred beliefs, but to stop the advancement of society as a whole.  The alternative realities they create will slow down technological improvements, impede advances in medicine and prevent the protection of our environment. 

Information preference bubbles can be ideal environments to nurture audiences pre-primed to accept narratives masquerading as news stories as well as disseminate misinformation or disinformation.  For example, assertions of migrants posing a looming smallpox epidemic threat were greeted with skepticism and frank derision in one group, while it is not hard to imagine that in others the identical claim might resonate and spur drastic reactions.

The reactions to the Orson Welles radio program suggests all is not lost when it comes to frightening news in the era of social media.  Certainly citizens can strive to become more discerning news consumers and judicious in deciding which stories to share.  Should we trust social media companies to protect us from anonymous trolls and veiled provocateurs?  Unfortunately, the speed at which fake accounts can be established (6) suggests it will be hard to police the new public square.  However, some dangers are now clearly foreseeable which makes implementation of active control measures essential before hypothetical worst case scenarios become manifest.  We ignore the synergistic threats of fake news and camouflaged social media accounts at our own peril.         

Will the next phase of our social media story be written by bigoted blowhards stumbling on a magical combination of circumstance, explosive words and images that fanned violent reactions?  In the end, it might make little difference whether social media terrorists are home-grown propaganda alchemists playing with fire or Al-Qaeda operatives.    

Blowhard

(1) A. Brad Schwartz. 2018.  Orson Welles and the Birth of Fake News.  The New York Times, 30 October 2018.  https://www.nytimes.com/2018/10/30/opinion/orson-welles-war-of-the-worlds-fake-news.html

(2) The National Institutes of Health.  https://www.niaid.nih.gov/diseases-conditions/smallpox

(3) Elizabeth Eaves.   The California Lawmaker Who Wants to Call a Bot a Bot.  Bulletin of the Atomic Scientists, 23 August 2018.  bit.ly/2BMOUKK

(4) NBC database https://www.nbcnews.com/tech/social-media/now-available-more-200-000-deleted-russian-troll-tweets-n844731

(5) Jessica Glenza.   Russian Trolls ‘Spreading Discord” Over Vaccine Safety Online.  The Guardian, 23 August 2018.  https://www.theguardian.com/society/2018/aug/23/russian-trolls-spread-vaccine-misinformation-on-twitter

(6) Siva Vaidhyanathan.   Why Facebook Will Never Be Free of Fakes.  The New York Times, 5 September 2018.  https://www.nytimes.com/2018/09/05/opinion/facebook-sandberg-congress.html

(7) Clint Watts.   Messing with the Enemy, HarperCollins.

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Puzzle Vision – Hyperactive Fruit Flies, Evolution and DARPA

 It is now accepted that the microbiome makes essential contributions to animal health.  But, do these resident microbes directly influence complex behaviors?  A study featured in Nature (1, 2) suggests that the activity of fruit flies (Drosophila melanogaster) is strongly influenced by the biochemical impacts of a gut bacterium.

It Only Takes One

The investigators used a classic ‘now you see it, now you don’t’ approach to demonstrate that fruit flies lacking their normal bacterial gut flora exhibited a hyperactive walking behavior.  Normal behavior patterns could be restored by replacing a single species of bacterium.  Going further, the investigators showed providing only one enzyme produced by the bacterium, xylose isomerase, reestablished normal behavior.

Capitalizing on their ability to manipulate fruit fly genetics, the scientists were able to explore this microbe-biochemistry-behavior nexus in more detail.  After activating neurons responsible for fly movement, they noted a specific neurotransmitter was associated with hyperactive-like walking activity and deduced how that behavior might be influenced by gut carbohydrate levels.  This work reveals fruit flies will provide a powerful experimental model system to clarify how the microbiome is intimately involved in mediating animal behaviors.

Extrapolation to the Future   

Could the fruit fly model offer insights into how our gut microbes influence human cognition and activities?  Maybe, but quite a bit more work remains just to decide how bacterial enzyme activity determines sugar levels and how those conditions cascade into neuronal signaling in fruit flies.  Nonetheless, having a genetically tractable and simple model of microbiome dynamics on host behaviors is cause for optimism that we may be able to understand how the far more complex human systems function as well.  And knowing such things might enable the creation of entirely new therapies to mitigate debilitating brain malfunction.  

Puzz1

 

The Pieces Fall in Place?

The potential implications of this basic research for human wellbeing are clear and I doubt that anyone would label this work as ‘dual-use research of concern.’  Engaged in solving specific puzzles scientists sometimes produce results with far-reaching ramifications.  Sure enough, we can see how the fruit fly microbiome might lead all the way to human medicine.  But, these same puzzle pieces of new knowledge might also fit in some surprising places. 

 

The U.S. Defense Advanced Research Projects Agency (DARPA) is supporting research that could culminate in a capacity to use insects to disseminate genetic alterations through single generations of still-growing crop plants (3-5).  The Insect Allies program may prove to be an ideal means to protect crops and prevent loss of life.  It is also easy to envision how these allies could be converted into threatening adversaries. 

Puzz3

How might fruit fly microbiomes connect to the DARPA Insect Allies work?  Let’s say it becomes feasible to field an army of insects to distribute gene drives through standing crops.  This strategy will be limited by the nature of the insects; how far they disperse, how active they will be under prevailing environmental conditions, etc.  Maybe it is too cold or too hot and the bugs just do not want to move.  Or maybe they really like feeding on their target plants and see no reason to leave once they are put in place.  Then knowing a few manipulations of the bug microbiome will make them hyperactive might be just the thing to ensure success.  Perhaps future field marshals of the bug army will transform their minions into gene altering berserkers by loading them up to their spiracles with antibiotics or xylose isomerase inhibitors or bacteria that antagonize microbiome species producing that enzyme.  My guess is that the paper by Schretter et al. has probably already made the rounds at DARPA and/or been featured at their journal club(s).   

Puzz4

Constant Evolution

Not long ago some baffling observations of repeated palindromic DNA sequences in bacteria were explained as the permanent records of a defense mechanism against virus infection.  And not long after that we saw some creative persons turn these bacterial CRISPR systems into a powerful gene altering tool and much more.  Science evolves, self-catalyzes and builds on its results.  Bits of knowledge lock into place here, there and elsewhere to reveal larger mosaics beyond anyone’s dreams or abilities to envision.  We have only a vague notion of where these projects will lead us.        

Puzz5

(1) Angela E. Douglas.   Gut Microbes Alter the Walking Activity of Fruit Flies.  Nature, 24 October 2018.  https://www.nature.com/articles/d41586-018-07080-y

(2) Catherine E. Schretter et al.   A Gut Microbial Factor Modulates Locomotor Behaviour in DrosophilaNature, 24 October 2018.  https://www.nature.com/articles/s41586-018-0634-9

(3) Emily Baumgaertner.   Viruses Spread by Insects to Crops Sound Scary.  The Military Calls It Food Security.  The New York Times, 4 October 2018.  https://nyti.ms/2OBMWCb

(4) G. Reeves et al. 2018.  Agricultural Research, or a New Bioweapon?  Science, 5 October 2018.  http://science.sciencemag.org/content/362/6410/35

(5) Statement from Dr. Blake Bextine, DARPA Program Manager for Insect Allies. https://www.darpa.mil/attachments/DARPA%20Response%20to%20Science%20Opinion%20Piece%20-%20Oct%204%202018.pdf

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The Ivory Tower and the Malignancy of Predatory Publishing

The academic world recognizes it has a problem.  Industry predators have created venues that mimic legitimate peer-reviewed journals, but publish anything submitted – for a fee (1, 2).  Some researchers may have been fooled into submitting manuscripts to these illegitimate journals, but it is clear that many have deliberately decided to exploit an opportunity to evade meaningful peer review (1, 2).     

A Sign of Deeper Problems

The emergence and enormous expansion of predatory journals is a sign things are amiss in the academic community.  ‘Publish or perish’ has long been the paramount rule and it is easy to envision how that might exact a toll on quality.  The old platitude about sizing up candidates for hiring and promotion by weighing a curriculum vitae in a literal sense sums it up well – the more publications, the more favorable the impression.  For those needing to bulk up a c.v. predatory journals are like anabolic steroids.  Intense competition for positions and grants, heavy demands on faculty time, a drive to achieve tenure or reach career advancement goals may tempt some to take such measures (1, 2). Persons passing off these pay-to-post publications as equivalent to peer-reviewed works are engaging in academic fraud.

A substantial fraction of people exploiting predatory journals might do so only to help themselves.  But, beyond allowing less qualified persons to enter and remain in academics, could there be larger ramifications?  The ‘reproducibility crisis’ of science, the concern that many studies cannot be replicated (3), may be exacerbated by generating a large body of un-reviewed publications of dubious merit.  Asked in a survey to speculate about the issues negatively impacting reproducibility, scientists again cited competition for positions and resources, pressures to publish along with time constraints (3).  The swift growth of predatory operations and the fact that knowledgeable parties constitute a significant portion of their customer base (2) is an unmistakable red flag of danger from a system under stress.

How Far Might This Cancer Spread?

Could the tentacles of this problem extend beyond academia?  It could be that there are (or will be) more temptations in play than the academic rewards for inflating a c.v.  Willful failures of a high-profile cancer investigator to disclose major competing financial interests (4) and ghost writing of papers by industry research underwriters (5) suggest that additional forces may come into play other than getting a few more manuscripts published.  Although the reputable journals have sometimes done a poor job patrolling these areas, perhaps journals with even more lax conflict-of-interest rules would offer less stressful and faster routes to credibility through results publication.  And for medical operations that appear to be unscrupulous (6), completely bogus or scientifically dubious publications may be nothing more than a means to mislead prospective customers into believing they are paying for research-validated treatments.        

Metastasis Beyond the Borders of Academe

Predatory publishing has prompted a great deal of discussion in academic fora and major news media outlets.  Educating faculty about the issue, offering guidelines to expose the hallmarks of predatory publications and creating ‘blacklists’ of known offenders to ensure persons evaluating professional credentials are not misled by fake publication list inflation will minimize the problems in the Ivory Tower.  Unfortunately, securing the Ivory Tower is only a partial solution to a much larger problem. 

Persons and organizations outside the sanction of academic institutions or funding agencies may be immune to traditional punitive measures.  Perpetrators of scientifically-camouflaged biomedical frauds, entities seeking to undermine faith in authority/social institutions for specific causes or with broader interests in sowing civic discord (7, 8) may soon discover predatory publications are extremely useful tools.  A failure to arrest the threat of predatory publishing operations may ultimately allow their impacts to spread and reverberate through the whole of society as well as our political processes.

Academic institutions, dedicated to research and education, have generally placed public outreach efforts on the lowest levels of their priority lists (9). When it comes to the threat posed by predatory publishing, the general public and academic community share urgent, common cause which makes mutual communication between the spheres essential.  Active engagement and leadership by the academic community to disseminate information about the issue along with strategies to combat the problem is now vital.  This is a good moment for the academic community to devise ways to reward public outreach efforts as has long been in vogue for producing long lists of publications very few people ever read.  Despite all its power and many impressive accomplishments, the Ivory Tower cannot stand by itself.       

ITower

 

(1) David Crotty.   Predatory Publishing as Rational Response to Poorly Governed Academic Incentives.  The Scholarly Kitchen, 28 February 2017.    https://scholarlykitchen.sspnet.org/2017/02/28/predatory-publishing-rational-response-poorly-governed-academic-incentives/

(2) Gina Kolata.   Many Academics Are Eager to Publish in Worthless Journals.  The New York Times, 30 October 2017.  https://www.nytimes.com/2017/10/30/science/predatory-journals-academics.html

(3) Monya Baker and Dan Penny.   1,500 Scientists Lift the Lid On Reproducibility.  Nature, 25 May 2016.  https://www.nature.com/news/1-500-scientists-lift-the-lid-on-reproducibility-1.19970

(4) Peter Sidaway.   Editorial – The Murky World of Disclosures.  Nature Reviews Clinical Oncology, 27 September 2018.  https://www.nature.com/articles/s41571-018-0106-z

(5) Matthew Warren.   Ghost Authorship Haunts Industry-funded Clinical Trials.  Nature, 9 October 2018.  https://www.nature.com/articles/d41586-018-06986-x

(6) Denise Grady and Sheila Kaplan.   F.D.A. Moves to Stop Rogue Clinics From Using Unapproved Stem Cell Therapies.  The New York Times, 9 May 2018.  https://www.nytimes.com/2018/05/09/health/fda-stem-cell-clinics.html

(7) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.  https://www.cnn.com/2018/08/23/health/russia-trolls-vaccine-debate-study/index.html

(8) Jennifer Kavanagh and Michael D. Rich.   Truth Decay.  RAND Corporation Research Report.

https://www.rand.org/pubs/research_reports/RR2314.html

(9) Chris Woolston.   University Tenure Decisions Still Gloss Over Scientists’ Public Outreach.  Nature, 4 October 2018.  https://www.nature.com/articles/d41586-018-06906-z

 

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The Perception Question – Will the DARPA Insect Allies Program Spark More Than Controversy?

The U.S. Defense Advanced Research Projects Agency (DARPA) has a need for speed.  Engineer-authors using gene drives to push DNA re-writes through crop plants are now forced to wait patiently for reproductive processes to slowly propagate their alterations.  Under some circumstances the leisurely pace of gene drive overwrite spread is just too slow to be helpful.  The Insect Allies Program aims to overcome that limitation by harnessing virus-transmitting bug hordes to disseminate genetic alterations through a single generation of still-growing crop plants (1).

The Double-edged Sword of Dual Use Research

The underlying rationale for Insect Allies research is a unique blend of beneficence and fear.  For example, being able to bolster the resilience of crops threatened by drought before they succumb might ultimately save many lives.  Countering emerging pest attacks by distributing precisely the most effective resistance genes could save money and decrease the needs for toxic chemical applications to protect crops.  The needs are many and a broad range of work clearly fits under the big tent of promoting the national security.    

Notwithstanding the benefits, the Insect Allies work has been stung by criticism from the scientific community (2).  This is not a deep technical critique of the research (which has yet to be published), the buzz is coming from scientists concerned about the near term implications of this work and its possible future ramifications.  Some scientists have expressed explicit fears that the capacity to create insect helpers to defend crops might be detoured easily into developing bioweapons to destroy them.  Therein lies the dilemma of this dual use research; work that yields benefits may also pave the way for producing new destructive armaments.  The DARPA program manager has responded to the criticisms (3), but the divisions are sharp.  Much of the debate involves opinions as to how others might react to the work, how it is being justified to the public and the wisdom of publishing results in the open literature.   

The Perception Question

Concerns over how the Insect Allies work is perceived are expressed throughout the critique (2).  One worry is that an unconvincing rationale for developing insect vectors and readily foreseeable offensive spin-off applications will inevitably fuel suspicions.  Past history suggests that adversaries will never accept any official U.S. government explanations that the Insect Allies program is not a potential threat.  In his book, Biohazard, Ken Alibek, a former leader of the covert Soviet Union bioweapons program, offered a blunt assessment of the ultimate impact of President Richard Nixon’s public renouncement of the use of deadly biological agents (4).  It was simply not believed and their efforts continued without pause.  The U.S. government has an unfortunate track record of authorizing the wide use of plant-destroying chemicals in armed conflict and engaging in disinformation efforts at the highest levels to manipulate public opinion of specific bioweapons threats (5).  It seems possible that others could look at the evidence, conclude it is impossible to ascertain U.S. intentions and take actions deemed necessary to protect their interests. 

Alarming Hypothetical Extrapolations

It is not a great leap to conclude the skills and experience acquired in developing gene alteration-transmitting insect armies might be applied directly to create plant destroying agents (2).  Perhaps the tools and techniques perfected to enlist insect vectors of plant viruses to execute genetic alteration missions could be extrapolated a bit further to envision an analogous concept involving mosquitoes and certain arboviruses.  Alphaviruses have been employed as gene vectors, the technology to produce and genetically modify them is well advanced (6).  Mosquito husbandry procedures have been developed by the military (5) and commercial processes, including mobile facilities, are being used today to mass produce genetically modified variants for disease transmission abatement research (7).  Will others piecing together information published in the public sphere and following new developments conclude mosquito-borne arboviruses engineered to debilitate food animals or human enemies are a feasible prospect?  Maybe those predisposed to question DARPA motives will construe this as just another example of the agency need for speed; food destruction is too slow, let’s hit the enemy faster. 

Mosq3

The Evergreen Justification

Frightening ideas may proliferate in a hothouse atmosphere of distrust and DARPA has done more than a fair job building its own unique mythos greenhouse.  As with many known agency projects, the Insect Allies work is bold and ground-breaking.  It is transparent in that the agency has promoted it to the public.  There seems little doubt positive publicity may build reliable support among the U.S. citizenry for this and future endeavors.   

  IMG_2647             

The notion we must stay ahead of potential adversaries has provided a powerfully compelling justification for many defense programs through the years.  However, when it comes to creating anxiety and a sense of urgency, DARPA is in a league of its own.  In a Nature article (8) describing the many concerns surrounding the use of new gene drive technology, one comment attributed to a DARPA geneticist was especially interesting. 

Security concerns may mean that DARPA needs to start working on the technology before guidelines are drawn up.” 

While this statement in no way suggests DARPA investigators would act irresponsibly, it does lend credence to the idea that regardless of what the broader scientific community is doing, agency scientists will ensure their gene drive research efforts are not impeded.  Any antagonists following developments in gene drive technology might conclude they understand what was revealed. 

In one sense the staying-ahead-of-our-rivals justification always works.  The problem is it always works for everyone.  It is easy to imagine technical advisors in other nations pointing to the statement above to muster support for corresponding programs.  Couple that with DARPA supporting clearly dual use research, a weak official rationale, sprinkle in a few frightening hypothetical extrapolation scenarios and we are all well on the way to enacting a self-catalyzed, self-fulfilling and maybe a little self-serving prophesy.  

And so, the race with no finish line begins.

(1) Emily Baumgaertner.   2018.  Viruses Spread by Insects to Crops Sound Scary.  The Military Calls It Food Security.  The New York Times, 4 October 2018.  https://nyti.ms/2OBMWCb

(2) G. Reeves et al. 2018.  Agricultural Research, or a New Bioweapon?  Science, 5 October 2018.  http://science.sciencemag.org/content/362/6410/35

(3) Statement from Dr. Blake Bextine, DARPA Program Manager for Insect Allies. https://www.darpa.mil/attachments/DARPA%20Response%20to%20Science%20Opinion%20Piece%20-%20Oct%204%202018.pdf

(4) Ken Alibek with Stephen Handleman.  1999.   Biohazard.  Random House.  p. 234

(5) Charles Piller and Keith R. Yamamoto.  1988.  Gene Wars.  Beech Tree Books, William Morrow and Company.  pp. 44, 70, 227

(6) Kenneth Lundstrom.   Alphaviruses in Gene Therapy.  Viruses 7(5):2321-2333.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452908/

(7) Lev Facher.   2018.  The Future of Genetically Modified Mosquitoes Could be in Mini, Moveable Labs.  PBS Newshour, 11 February 2018.  https://www.pbs.org/newshour/science/the-future-of-genetically-modified-mosquitoes-could-be-in-mini-moveable-labs

(8) Heidi Ledford.   2015.  Caution Urged Over Editing DNA in Wildlife (Intentionally or Not).  Nature, 4 August 2015.  https://www.nature.com/news/caution-urged-over-editing-dna-in-wildlife-intentionally-or-not-1.18123

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Eggon’s Game

 

You are about to battle an army of trolls and bots.  Masters of disguise and rapid reproduction, the enemy run rampant.  The future – for your nation and your children – is at stake.  The war has begun.

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The lines above look like a stale premise for an unoriginal computer game.  However, in an unfortunate instance of life imitating art, too much of it is true.  A new mode of war has been launched and everyone will be impacted by it.       

You’re in the Army Now

The all-volunteer military has been around for over 45 years, but many U.S. citizens probably remember the selective service process of involuntary conscription, informally known as ‘the draft,’ the armed forces once used to fill their ranks.  For millions of young American men that process culminated with a written greeting ordering them to report for induction into the armed forces.           

Foreign government information influence operations against American interests have been conducted through social media and experts anticipate more campaigns (1, 2).  These systematic endeavors to manipulate the public through social media channels were initially overlooked by intelligence agencies (1).  However, the potential implications of what must be acknowledged as a brilliant disinformation and distraction strategy are staggering.  Everyone, users of social media or not, will be involved in this internet influence war or impacted by the outcomes.  Like it or not, all of us have been drafted into battle. 

The Strategic Situation

Government propaganda has long been used by and against American citizens and the situation today is a true golden age for public opinion manipulators.  Social media bypass the traditional mass media gatekeepers and allow essentially unfiltered, direct, access to audiences.  In addition, the information flow follows an unprecedented interactive pattern; social media make each person potentially self-empowered instant communications propagators.  Under the right circumstances information may be spread through electronic chain reactions without any regard for its accuracy or origins.    

In a deeply divided nation with closely contested elections, covert influence operations that alter a comparatively few votes may produce outsized impacts.  Social media are ideal political influence tools for foreign operatives because they can participate from afar while concealing their true identities.  What has been most surprising is the revelation that the actual scope of foreign social media influence operations extended far beyond direct U.S. electioneering efforts.  Generating civic controversy seems to be a top priority and social media troll farms and bots industriously stir it up wherever they find it (3-7).  From vaccination battles, to movies, to Supreme Court nominee preferences, the method seems to have been to sow discord into an already divided public square and let human nature take over.  Under some circumstances, confirmation bias coupled with an ability to forward items through social media spreads inflammatory information widely.  Our adversaries know the issues, our intrinsic weaknesses and how to use the astonishing power of social media platforms very well.

Eggon2

 

The Implications

In his book, Messing with the Enemy, Clint Watts outlines some of his counterterrorism exploits which employed social media (8).  His experience and insights are fascinating reading, but one of the most thought-provoking ideas he has presented is the notion that we should brace for a proliferation of troll farm-like influence operations.  We will soon exist in a social media environment in which every political interest group, corporation, or self-actualized individual will be able to operate their own information management – warfare – services (9).  It is now clear that social media are potentially far more powerful mass mind manipulation tools than many of us realized.  Mr. Watts reveals that terrorists have been adept at exploiting new technologies and social media (8).  With clear demonstrations of what can be achieved using only social media tools, how long will it be before they devise ways to harness the forces of swift, uncensored communications to unleash 9/11 style mayhem?

The capacity for users to specifically select and exclude information sources has created “preference bubbles” (8) enabling many in the most networked generation in history to exist happily in a peculiarly impoverished isolation.  Information exclusion may foster the flowering of alternative facts and the confusion or political divisions the presence of co-existing, but largely non-communicating information subcultures could sow in the greater civil society are staggering (10).  De facto information segregation has been achieved, meaning foreign agencies seeking to undermine national unity need only keep the subgroups agitated. 

The scientific community has yet to recognize that social media tools in combination with other developments such as the rise of predatory publishers pose an extraordinary potential danger to research and technological development (8).  Those bent on undermining respect and faith in public institutions and fact-based decision making processes have ideal mechanisms at their disposal to carry out their attacks.

Recognizing the Situation

Who was that person on Twitter you crossed swords with over the relative merits of The Last Jedi?  Was it even a human being you engaged (5, 6)?  With social media platforms generally flummoxed over the unanticipated uses of their systems as well as being hard pressed to simply eliminate fake accounts and bots, users are on their own.  Some guidelines about how to evaluate the reliability of on-line information and combat disinformation campaigns have been created (1, 11). Now that social media environments have become battlefields, recognizing if and when you are being egged on into playing someone else’s game has suddenly become important.      

 

Sucker2 

(1) Tim Mak.   What Can Citizens Do to Fight Foreign Disinformation Campaigns? NPR Morning Edition, 1 October 2018.  n.pr/2DLa1yg

(2) Laurie Segall.   Facebook’s Former Security Chief: US Elections at Risk of Being ‘World Cup of Information Warfare.’  CNN, 4 September 2018.   https://money.cnn.com/2018/09/04/technology/us-elections-disinformation-alex-stamos/index.html

(3) Carolyn Y. Johnson.   Russian Trolls and Twitter Bots Exploit Vaccine Controversy.  The Washington Post, 23 August 2018.  https://www.washingtonpost.com/science/2018/08/23/russian-trolls-twitter-bots-exploit-vaccine-controversy/?tid=ss_tw&utm_term=.35ee7afa7cc9

(4) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.  https://www.cnn.com/2018/08/23/health/russia-trolls-vaccine-debate-study/index.html

(5) Chris Taylor. “Last Jedi” Hate Tweets Were Weaponized by Russia, Says Study.  Mashable, 2 October 2018.  https://mashable.com/article/the-last-jedi-rian-johnson-russian-trolls/#swQy2fpUyuqA

(6) Max de Haldevang.   Russian Trolls and Bots Are Flooding Twitter With Ford-Kavanaugh Disinformation.  Quartz, 2 October 2018.  https://qz.com/1409102/russian-trolls-and-bots-are-flooding-twitter-with-ford-kavanaugh-disinformation/

(7) NBC database https://www.nbcnews.com/tech/social-media/now-available-more-200-000-deleted-russian-troll-tweets-n844731

(8) Clint Watts.   Messing with the Enemy, HarperCollins.

(9) Clint Watts.   How Every Campaign Will Have a Troll Farm of its Own.  The Daily Beast, 9 April 2018. thedailybeast.com/how-every-camp…

(10) Jennifer Kavanagh and Michael D. Rich.   Truth Decay.  RAND Corporation Research Report. https://www.rand.org/pubs/research_reports/RR2314.html

(11) Steve Inskeep.  2016.  A Finder’s Guide to Facts.  NPR, 11 December 2016.                      https://www.npr.org/2016/12/11/505154631/a-finders-guide-to-facts

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One at a Time – Precision Attacks With Deadly Mass Casualty Agents

Multiple lines of evidence suggest the deadly nerve agent known as Novichok was used to attack persons in Great Britain.  Charges and denials are swirling, but U.K. officials have traced back events in sufficient detail to issue criminal indictments against two suspects (1).   

Originally produced for use against NATO military units (2), the victims of two separate (probably linked) poisoning events in Salisbury currently known to involve Novichok have all been civilians, although some were clearly not so ordinary.  There is growing suspicion this military nerve agent has been unleashed more than once on British soil (2).

Pinpoint Applications of Mass Casualty Agents

The Novichok story might sound familiar; it is reminiscent of the shocking assassination of North Korean leader Kim Jong-un’s half-brother in a busy Malaysian airport (3).  Presumed to have been contaminated with the nerve agent designated as ‘VX’ sometime during two consecutive, minor, physical assaults, Kim Jong-nam was dead only minutes later. 

VX is also a fast-acting nerve agent developed as a military weapon (4).  Deliverable by several methods and able to penetrate the skin, it disrupts nervous system transmission leading to respiratory failure. Kim Jong-nam seems to have died after the oily liquid form was smeared on his face.  The odd nature of the attack – sequential assaults in short order by two women – may reflect the extreme danger posed by active VX agent.  It is possible that each attacker smeared on one of two separate components that only become deadly when combined (5).  VX is considered a weapon of mass destruction and was designed to be environmentally persistent (4, 5), making it fortunate that more persons did not die in this event. 

Another Poisoning?

The situation is unclear, but doctors treating Pussy Riot activist, Pyotr Verzilov, after he mysteriously lost his sight, speech and mobility speculate he may have been poisoned (6).  Details are still sketchy and although the symptoms described for Mr. Verzilov do not suggest another Novichok incident, the attack on former spy Sergei Skripal and his daughter have fueled conjecture (6).         

Are We Entering the Era of Highly Personalized Attacks?

To someone seeking to get away with murder, few methods could be better than a poison which mimics death due to a natural cause.  Novichok fits that bill because a single person discovered dead after exposure to the agent could easily be presumed to have suffered a fatal heart attack (2).  However, the tragic events in Salisbury reveal a perfect crime is not guaranteed and the lives of innocent bystanders may be threatened as well.

Making the assumption that perpetrators of chemical attacks intended to kill or injure only targeted persons, perhaps there are alternatives better than repurposing persistent nerve agents for small-scale operations.  Although also conceived as mass casualty agents, toxins developed for the purposes of biological warfare (7, 8) might be better suited to precision attacks that impact the intended target exclusively without creating a general environmental transmission hazard (8).  Toxins harnessed for use as unconventional warfare agents sometimes create naturally-occurring disease outbreaks and have a latency period before onset (7, 8) which may enable attackers to camouflage their activities or plausibly deny involvement.  In addition, toxin diseases are non-contagious which means health care workers rushing to aid victims will not be caught up in an epidemic (8).   

Target2

Botulinum is a neurotoxin responsible for the deadly paralytic disease botulism (7, 8) and has been produced as a biological warfare agent (8).  Although several forms of the natural disease are known, this toxin is most typically ingested in foods that were preserved improperly (7, 8).  Victims will exhibit a descending (head downward) flaccid paralysis which can culminate in respiratory failure without medical intervention.  Perhaps you have heard of Botox?  That is botulinum toxin diluted for safe medical use.

What Will We See?

The apparent poisoning of Mr. Verzilov will be interesting to follow.  Some of the symptoms reported in the press seem consistent with botulinum poisoning and we must await a definitive diagnosis to see if that speculation is correct.  Other reports suggest formerly strict taboos against the use of toxin agents may have loosened.  Perhaps we will soon have an unwelcome revelation the world has become a little more dangerous for some of us.   

 

(1) Richard Péres-Peña and Ellen Barry.   2018.  U.K. Charges 2 Men in Novichok Poisoning, Saying They’re Russian Agents.  The New York Times, 5 September 2018. https://www.nytimes.com/2018/09/05/world/europe/russia-uk-novichok-skripal.html

(2) Ellen Barry and Ceylan Yeginsu.  2018.  The Nerve Agent Too Deadly to Use, Until Someone Did.  The New York Times, 13 March 2018.  https://www.nytimes.com/2018/03/13/world/europe/uk-russia-spy-poisoning.html

(3) Kyle Swenson.   2017.  A Gruesome North Korean Murder Plot: Trial Sheds New Light on Assassination of Kim Jong Un’s Brother.  The Washington Post, 17 October 2017.  https://www.washingtonpost.com/news/morning-mix/wp/2017/10/17/the-gruesome-nerve-agent-assassination-of-kim-jong-uns-brother/?utm_term=.6cabefd313f8

(4) U. S. Centers for Disease Control and Prevention. Facts About VX.  https://emergency.cdc.gov/agent/vx/basics/facts.asp

(5) Justin McCurry.   2017.  What is the VX Nerve Agent That Killed North Korean Kim Jong-nam?  The Guardian, 24 February 2017.  https://www.theguardian.com/world/2017/feb/24/what-is-vx-nerve-agent-killed-kim-jong-nam-north-korea

(6) Christopher F. Schuetze and Melissa Eddy.   2018.  Pussy Riot Activist May Have Been Poisoned, German Doctors Say.  The New York Times, 18 September 2018. https://www.nytimes.com/2018/09/18/world/europe/pussy-riot-activist-poisoning.html

(7) Peter D. Anderson.   2012.  Bioterrorism: Toxins as Weapons.  Journal of Pharmacy Practice 25(2):121-129.

(8) Tamar Berger et al.   2016.  Toxins as Biological Weapons for Terror – Characteristics, Challenges and Medical Countermeasures: A Mini-Review.  Disaster and Military Medicine 2:7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330008/

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