Synthetic Genetic Shakespeares

Examining the implications of science and technology


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.

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.       



(1) David Crotty.   Predatory Publishing as Rational Response to Poorly Governed Academic Incentives.  The Scholarly Kitchen, 28 February 2017.

(2) Gina Kolata.   Many Academics Are Eager to Publish in Worthless Journals.  The New York Times, 30 October 2017.

(3) Monya Baker and Dan Penny.   1,500 Scientists Lift the Lid On Reproducibility.  Nature, 25 May 2016.

(4) Peter Sidaway.   Editorial – The Murky World of Disclosures.  Nature Reviews Clinical Oncology, 27 September 2018.

(5) Matthew Warren.   Ghost Authorship Haunts Industry-funded Clinical Trials.  Nature, 9 October 2018.

(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.

(7) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.

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

(9) Chris Woolston.   University Tenure Decisions Still Gloss Over Scientists’ Public Outreach.  Nature, 4 October 2018.




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. 


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.   


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.

(2) G. Reeves et al. 2018.  Agricultural Research, or a New Bioweapon?  Science, 5 October 2018.

(3) Statement from Dr. Blake Bextine, DARPA Program Manager for Insect Allies.

(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.

(7) Lev Facher.   2018.  The Future of Genetically Modified Mosquitoes Could be in Mini, Moveable Labs.  PBS Newshour, 11 February 2018.

(8) Heidi Ledford.   2015.  Caution Urged Over Editing DNA in Wildlife (Intentionally or Not).  Nature, 4 August 2015.


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.


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 influence 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 in discussions 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.


Ibfo war

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.      



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

(2) Laurie Segall.   Facebook’s Former Security Chief: US Elections at Risk of Being ‘World Cup of Information Warfare.’  CNN, 4 September 2018.

(3) Carolyn Y. Johnson.   Russian Trolls and Twitter Bots Exploit Vaccine Controversy.  The Washington Post, 23 August 2018.

(4) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.

(5) Chris Taylor. “Last Jedi” Hate Tweets Were Weaponized by Russia, Says Study.  Mashable, 2 October 2018.

(6) Max de Haldevang.   Russian Trolls and Bots Are Flooding Twitter With Ford-Kavanaugh Disinformation.  Quartz, 2 October 2018.

(7) NBC database

(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.…

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

(11) Steve Inskeep.  2016.  A Finder’s Guide to Facts.  NPR, 11 December 2016.            


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).   


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.

(2) Ellen Barry and Ceylan Yeginsu.  2018.  The Nerve Agent Too Deadly to Use, Until Someone Did.  The New York Times, 13 March 2018.

(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.

(4) U. S. Centers for Disease Control and Prevention. Facts About VX.

(5) Justin McCurry.   2017.  What is the VX Nerve Agent That Killed North Korean Kim Jong-nam?  The Guardian, 24 February 2017.

(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.

(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.


CIA Operation Brain Drain – The Strange Case of the Vomiting Chaperones

In his book Spy Schools: How the CIA, FBI and Foreign Intelligence Secretly Exploit America’s Universities (1) Daniel Golden explains how academia is a prime territory for espionage.  Involving much more than conducting direct spy vs. spy intrigues, the hidden hands of the intelligence community operatives know very well how the academic research enterprise works and how to manipulate the system to achieve specific agency goals. 

The CIA expended millions stealthily underwriting and organizing international scientific conferences.  In addition to facilitating communication and networking among researchers, these meetings had another, carefully hidden, agendum –  putting key Iranian nuclear scientists into situations where undercover CIA agents might persuade them to defect.  A substantial number, perhaps most, of the researchers in attendance may never have suspected they participated in events specifically organized by and for the benefit of the CIA.  And that was exactly how the veiled operatives wanted it.     

Mr. Golden details how a scientific conference was staged in support of a covert effort to impede Iranian nuclear weapons development known as “Operation Brain Drain.”  Aware of the risk of defections, the Iranian government took active measures to ensure scientists attending international conferences were chaperoned.  Getting past these diligent minders apparently necessitated some creative exploits.  Mr. Golden’s reporting offers a glimpse into an amazing scheme CIA operatives apparently used to spring free a targeted scientist for their approach.

“The CIA officer assigned to the case might pose as a student, a technical consultant or an exhibitor with a booth. His first job was to peel the guards away from the scientist. In one instance, kitchen staff recruited by the CIA poisoned the guards’ meal, causing massive diarrhea and vomiting. The hope was that they would attribute their illness to airplane food or an unfamiliar cuisine.”

[An excerpted, edited version of content (2) from Mr. Golden’s book including the passage quoted above is available here ]  

And How Exactly Did They Manage That?

The deliberate food poisoning spy caper is fascinating and troubling.  How did they do it?  As it happens one potential culprit fits the diarrhea and vomiting profile almost exactly – staphylococcal enterotoxin.  Produced by the bacterium Staphylococcus aureus, under the correct circumstances this protein can produce a sudden-onset and intense food poisoning characterized by vomiting and diarrhea.  This type of food poisoning comes on fast, in a matter of 30 minutes to a few hours, and runs a furious course that is usually over in a day (3, 4).  The disease is self-limited, will not respond to antibiotics and not is transmissible to others.  Large common source epidemics due to S. aureus food poisoning are unfortunately common.   


S. aureus food poisonings usually require a specific sequence of events to unfold (3). The bacterium must first be inoculated into food by careless handling. Many of us harbor this species without ill effect on our skin and nasal passages.  Once the food is inoculated it must be allowed to stand without refrigeration for a few hours.  This allows the bacteria to grow and produce the toxin responsible for the disease signs and symptoms.  After that growth period persons consuming the food will ingest the already-formed toxin molecules and become ill quickly.  So, one way to deliberately produce Staph food poisoning in your target would be for kitchen staff to sprinkle live bacteria on the right foods, let that material marinate a few hours and then deliver it.  Clearly it would be possible to do such things, but it turns out there is a much easier way to go about this process.  S. aureus food poisoning is an intoxication and once the toxins have been produced and ingested living bacteria are no longer needed for the disease process to run its full course.  Bio-weaponeers learned long ago to purify the toxin and cut the living bacteria middlemen out of an attack.            

Staphylococcal enterotoxin B (SEB) was produced as a biological warfare agent intended to debilitate targets (5, 6).  The agent is effective at extremely low doses, is colorless and imparts no odors or objectionable tastes to foods.  In addition, SEB is extremely potent and extraordinarily resistant to inactivation by heat or digestive processes, meaning tiny amounts spiked into food will be entirely sufficient to induce sure, swift and severe disease.  Robust, easy to produce, easy to hide, effective at unimaginably low doses and undetectable by the victims, SEB is an ideal attack agent with the added benefit of plausible deniability.  Accidental food poisoning events due to S. aureus are common enough that in the event the source of the fabricated disease outbreak is identified such findings are unlikely to raise great suspicions (5).  For someone bent on surreptitiously poisoning restaurant food and obtaining results within a predictable, short, time frame, SEB might be the weapon of choice.


Where Are We?

So, three cheers for the amazingly resourceful CIA operatives for devising a unique way to accomplish their Operation Brain Drain mission.  Or are a few questions regarding the technical details of that delicate undertaking in order?

It is not known how CIA operatives induced sudden vomiting and diarrhea attacks in certain Iranian attendees of a scientific conference.  The description of events is suggestive a toxin like SEB could have been used, but does not prove that allegation.  However, because the Biological Weapons Convention explicitly forbids the development, acquisition or possession of toxins for non-peaceful activities (7), evidence or claims even suggesting SEB could have been used to debilitate persons raise serious questions.    

The CIA history with bio-warfare toxins is particularly troubled.  In 1975 the agency admitted a willful refusal to comply with orders to destroy such agents (8).  Worse, despite having no authority to conduct operations using chemical and biological weapons, the agency was discovered to possess toxin stockpiles adequate to kill hundreds of thousands (8).  One thing to keep in mind when it comes to purified toxins; they are outrageously powerful.  That means it was and is feasible to store a few grams of some toxins that could possibly kill thousands of persons in a desk drawer. 

Questions about the operational details of a toxin attack mount up quickly.  Where and how would the CIA acquire toxin stocks?  Who certified their potency?  After spending substantial sums to front a conference, you may wish to be absolutely certain that if the entire operation hinges on making chaperones sick, your reagents are up to the task.  What deliberative process went into weighing the risks and benefits of such a course of action? It is important to recognize that SEB can do more than create temporary gastrointestinal upsets, under the right circumstances it can act as a super-antigen able to induce lethal multi-organ system failure (5, 6).  If SEB was used, who estimated the proper dose that would quickly debilitate, but not kill, the targets and ensured the kitchen staff recruited for the job got that critical detail correct?   Finally, what person(s) approved the action? 

On one hand, the many questions and difficulties suggest that the CIA would not seek to acquire and deploy SEB.  On the other hand, the CIA has an unfortunate legacy of apparently not being overly concerned about the consequences of some activities.  In a time of ‘fake news’ would an official denial serve to put doubts to rest?  Disinformation released in the service of overarching intelligence agency goals and seeded into mainstream news sources is nothing new (8). 

Well, They’re Doing It

The reporting by Daniel Golden on Operation Brain Drain instantly suggested the possibility an enterotoxin might have provided the means to quickly, but temporarily, debilitate the chaperones of nuclear scientists targeted by the CIA.  Almost certainly, other persons with more expertise in clandestine operations would have noted that possibility as well. 

In the dark world of intelligence operations maybe whether or not SEB was actually used to incapacitate people is not as important as suspicions it might have been.  Fears that adversaries are violating agreements and justifications based on a need to safeguard national security could provide leverage to overturn long-honored prohibitions.  Intelligence agency personnel compete in their jobs like everyone else (1), perhaps somewhere this story or ones like it are being used to explain why new covert initiatives and actions are needed (6).  The ‘they’re doing it’ rationale and compelling calls to immediate action might take us where no one wants to go.  Maybe they already have.     

Special thanks to blogger/author Jeffrey Kaye (@jeff_kaye) for a Twitter post that first drew my attention to the paper and book by Daniel Golden.   


 (1) Daniel Golden.   Spy Schools: How the CIA, FBI and Foreign Intelligence Secretly Exploit America’s Universities. Henry Holt and Company.  (Chapter 8, “Bumps and Cutouts”)

 (2) Daniel Golden.   How the CIA Staged Sham Academic Conferences to Thwart Iran’s Nuclear Program., 10 October 2017.

(3) Maria Angeles Argudin et al.   Food Poisoning and Staphylococcus Enterotoxins.  Toxins 2(7):1751-1773.

(4) Centers for Disease Control and Prevention. Staphylococcal (Staph) Food Poisoning.

(5) Ejem Ahanotu et al.   Staphylococcal Enterotoxin B as a Biological Weapon: Recognition, Management and Surveillance of Staphylococcal Enterotoxin.  Applied Biosafety 11(3):120-126.

(6) Bettina C. Fries and Avanish K. Varshney.   2013.  Bacterial Toxins – Staphylococcal Enterotoxin B.  Microbiology Spectrum 1(2)

(7) Gabrielle Tarini.   2016.  Keeping the Biological Weapons Convention Relevant.  Bulletin of the Atomic Scientists, 1 November 2016.

(8) Charles Piller and Keith R. Yamamoto.  1998. Gene Wars.  Beech Tree Books, William Morrow and Company.


Manufacturing Science – Will Hoaxers Cook the Books With Synthetic Data?

Craig Foster and Sarenna Ortiz writing in Skeptical Inquirer just over one year ago put forth a fascinating observation (1).  Analyzing how anti-vaccination proponents presented evidence for their hypotheses, the authors noticed that although a critical scientific work which initiated much debate was later denounced as fraudulent, the argument did not die after that paper was retracted.  Instead, anti-vaccination advocates began offering other published works they claimed supported the same basic idea as the retracted work – quite a few of them.  Ultimately, a strategy seems to have evolved to overwhelm critics by citing any and as many studies as possible, without regard for quality or relevance, that seem to support an assertion.   Internet access and social media have combined to enable easy mining of the scientific literature as well as allowing both sides of the controversy to present the results to receptive, if not always judicious, audiences (1). 

Seeking the Imprimatur

A counterintuitive lesson from the Foster and Ortiz article is that efforts to locate and highlight irrelevant research to bolster pseudoscientific claims tacitly underscore the central, although cryptic, significance of science to the discussions (1).  Those most able to utilize the scientific literature to validate their positions may be taken by the public to have offered a superior rationale for their assertions. 

Scientific research is data driven, but professional researchers may make errors or be taken in completely by hoaxes like anyone else.  The Piltdown Man story (2) reminds us that physical evidence can be manufactured and presented in ways that are almost irresistible.  The hard lesson here is that a clever scheme combined with confirmation bias can so mislead experts it may take a long time to realize what has happened.  To help prevent errors and root out fraud the scientific community employs a system of peer review to evaluate research project proposals and publications.  No system is perfect, but publication of research in peer-reviewed journals is the general certification of quality most professional researchers will seek for their work.

Author Sharon Hill has described the complex sequence of events that unfolded around a high-profile Bigfoot research project and principal investigator, Dr. Melba Ketchum (3).  This was a sensational story featuring amazing claims with stunning potential ramifications.  First came a tantalizing hint a manuscript describing forensic evidence of the creature known commonly as Bigfoot was undergoing peer review at a mainstream scientific journal.  The logical deduction from that tidbit was investigators had to have something solid in hand to submit a paper for peer review.  So, was this work going to finally provide scientific proof these legendary creatures were real?  The pot boiled vigorously for months until it became clear the alleged Bigfoot evidence was a hopeless jumble.  In the end, this debacle became a cautionary tale of lost credibility and a warning to the scientific community.

Seeking recognition from the scientific community, Dr. Ketchum and her co-workers apparently submitted a manuscript to mainstream scientific journals (3).  On receipt, among other things, the journal editors would have solicited confidential assessments from experts regarding its scientific merits, i.e., obtained a peer review, to determine whether it was suitable for publication.  At some point it seems the efforts to get the Bigfoot DNA paper accepted by mainstream scientific journals went totally off the rails.  However, the work was published – as the first offering in a new journal of sketchy provenance (3), a situation which enabled the investigators to circumvent the insurmountable roadblock of meaningful peer evaluations.  Ultimately, that paper did not withstand the scrutiny of the interested public.  A cursory look at the data and methods confirmed it was clearly unsuitable for publication in a scientific journal with even poor editorial and ethics standards. 

The Customers Always Write

Predatory publishers (4) are a fast emerging challenge to the scientific community.  Pay-to-play operations may enable authors to publish works that undergo either perfunctory or no peer reviews.  That means predatory publishers are not acting as quality assurance gate keepers, a role customarily performed through explicit scientific journal editorial policies and procedures. Predatory journals are deceptive imitations of legitimate operations and could mislead many into thinking articles appearing in them are equivalent in quality to those published in peer-reviewed publications.  Worse, loathe to impose any standards on their author/customers, it seems likely these opportunistic journals will have no interest in receiving post-publication comments and critiques or incentive to create effective mechanisms to retract erroneous or fraudulent papers.  The flood gates are open and the trash that spills through may pollute the scientific literature on the internet forever.                      

Find – or Fabricate – an Audience Through Social Media

The rise of social media is giving content creators total freedom to craft messages and distribute them to an audience directly without the participation of mass media middlemen (5).  Users have long been able to select mass media content, but now social networks empower them to easily propagate favored information through their personal networks.  Because social media have made everyone a publisher, the traditional news media no longer have the power to dictate what stories are pursued and disseminated in the way they did not long ago.  In addition, social media services are unwilling or unable to act as information quality gatekeepers.  Deliberately insulated from disturbing materials (5), preference-based information bubbles composed of like-minded persons are for all practical purposes beyond the influence of mainstream media gate keepers and opinion leaders (6).  For some, this potentially chaotic information environment is an extraordinary opportunity.   

Cooking the Books

Social media have been harnessed by shadowy groups intent on sowing civic discord (7) and these efforts may be expanding in multiple directions (8, 9).  It seems safe to assume that for any parties intent on creating turmoil, the ends justify the means, so there would seem to be few concerns over seeding completely bogus information into social networks. 

Perhaps we will soon see a new way for chaos agents to foster the activities of pseudoscience advocates.  Instead of being forced to mine the scientific literature for legitimate publications of dubious relevance (1), perhaps pseudoscience advocates will one day discover exactly what they need sprinkled throughout the new universe of predatory journals.  Scientific papers, bogus, purpose built to mislead and hard to easily refute, would be constructed so as to seem to offer precisely what someone hoping to discredit authentic research could ever dream of finding, which may make them almost irresistible.  Provocative content complete with links to bogus research injected into a few select social networks at opportune moments might generate self-catalyzing cascades of fake science transmission.  A few pre-positioned fake papers set in place with minor expense outlays could enable troll farm operations (9) to pollute legitimate content and fuel rancorous conflagrations of utterly confusing controversy. 

The scientific community must devise ways to identify predatory publishers, prevent researchers from falling prey to, or intentionally using, faux journals and help the public understand how these deceptive organizations work.  The potential threat of systematic efforts to cook the scientific books to mislead or provoke the public must not be underestimated.

Cook the Books


The Resurrection of P. T. Barnum     

The investigators claiming DNA evidence of Bigfoot (3) were unable to prove their assertions, but they do not seem to have been hoaxers.  Perhaps we now need to be alert to efforts to deceive the public with convincing DNA sequence data constructed out of whole cloth.  If would be hoaxers are clever, anticipate what findings are necessary to establish a claim and make good use of existing sequences from databases, peer reviewers, if there are any, may be confronted with data that is not easily dismissed.  Scientific research and peer review are predicated on trust and reviewers ordinarily receive and evaluate experimental results, not raw samples.  A well-conceived hoax that checks the proper confirmation bias boxes might require quite a while to be sorted out.

Undoubtedly, something as paradigm shaking as an announcement of scientific proof Bigfoot is real, would prompt calls for independent assessments by an unaffiliated laboratory.  But, would they be heeded?  Perhaps in some isolated social media networks such concerns and calls may never be seen or noted.  With persons getting so much news of their specific choosing from social networks, a hoaxer may be able to glean a nice living speaking to enthusiastic niche audiences who hear nary a word to the contrary because they simply refuse to entertain such notions.  The prospect of eliciting expressions of scorn and ridicule from the scientific community may be no deterrent for persons operating entirely outside the realm of official sanction.  For anyone attempting to spark battles between citizens, outraged statements from scientists and skeptics might be used as objective indicators of success.   

(1) Craig A. Foster and Sarenna M. Ortiz.   Vaccines, Autism and the Promotion of Irrelevant Research: A Science-Pseudoscience Analysis.  Skeptical Inquirer 41(3):44-48, May/June 2017.

(2) Piltdown Man. Natural History Museum.

(3) Sharon Hill.   The Ketchum Project: What to Believe About Bigfoot DNA ‘Science.’  Skeptical Briefs 23.1, Spring 2013.

(4) Alex Hern and Pamela Duncan.   Predatory Publishers: The Journals That Churn Out Fake Science.  The Guardian, 10 August 2018.

(5) Jason Gainous and Kevin M. Wagner.   Tweeting to Power: The Social Media Revolution in American Politics. Oxford University Press, 2013.

(6) Jennifer Kavanagh and Michael D. Rich.   Truth Decay.  RAND Corporation, 2018.

(7) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.

(8) Laurie Segall.   Facebook’s Former Security Chief: US Elections at Risk of Being ‘World Cup of Information Warfare.’  CNN, 4 September 2018.

(9) Clint Watts.   Messing with the Enemy. HarperCollins, 2018


Public Outreach During a Global Information War Era

Scientific advances occasionally disturb the public.  In his book, Frankenstein’s Footsteps, Jon Turney describes how researchers forced to address ethical concerns have successfully defused confrontations (1).  Truthfully reassuring citizens the real world impacts of their discoveries still lay in a hypothetical future, researchers called for dialogue with the public – at an unspecified, more appropriate time.   While that reasonable request defused then current crises, the unfortunate outcome was delaying discussions often ended up effectively suppressing communication between scientists and the general public.  The times have changed and the ‘you don’t need to worry yet, we can talk about this later’ days are gone.  Putting off difficult discussions with the public about ethical dilemmas posed by some research is no longer advisable.  In fact, it is no longer possible.       

We Will Discuss It Now

Biomedical research has recently yielded genome editing tools of immense potential power and obvious, practical utility.  The pace of advance has been so swift that even scientists have expressed anxiety about potential impacts and how to proceed judiciously (2).  Driven by rumors of impending announcements of genetic editing of human embryo genomes, perhaps anticipating public backlash to that dramatic milestone, leading scientists convened a meeting to assess the situation and promote immediate efforts to develop guidelines for future genome editing research (2).

The scientific community conducted a similar effort in 1975 with a conference at Asilomar (California) (2) to decide how to regulate recombinant DNA technology research.  While there were concerns certain experiments might pose dangers, the issues examined mainly involved creating guidelines for the safe conduct of operations and implementation of adequate containment procedures in research labs.  For the most part, the discussions about regulating recombinant DNA research remained within the scientific community.  The 1975 Asilomar meeting is held forth as a model of responsible scientific community self-governance, but it must be remembered it took place in simpler times when the major direct conflict-of-interest for many participants was active involvement in that research area.  Looking back at that Asilomar conference a decade later, organizer and Nobel laureate Paul Berg warned that the blurring separations between corporate and academic boundaries could complicate future efforts to control biotechnology development (3).  Some of his concerns have come to pass.     

There is now no easy way to avoid many ethical debates by declaring them premature because it is clear several new gene editing technologies are already being commercialized.  Several accomplished scientists at the forefront of gene editing research have raced to launch companies to exploit the new tools and latest research findings.  In addition, prestigious research institutions have engaged in a bitter legal battle over the patent rights to key gene editing technologies, clinical trials of therapies utilizing gene editing are underway and more are planned. A modern age gold rush is on and there is nothing hypothetical about it.      

Here Be Dragons

Several leading scientists involved with gene editing research and development have been making extraordinary efforts at public outreach.  Writing books, producing articles and appearing on broadcast media they have been explaining the issues to both the scientific community and the general public.  Other researchers will need to support them in these public outreach endeavors.  Equally important, academics may be accustomed to lecturing, but the communications cannot remain a one way process – the involved scientific community must also make efforts to hear the concerns of the public and respond to them in good faith.  To their credit, some have begun such work. 

The good news is that social media empower scientists to communicate directly with the public with unprecedented ease and reach.  However, these places could be potentially dangerous to scientists suddenly intent on engineering public opinion as well as genomes.  An information war has been raging on social media for several years and they will find themselves in the middle of it.

Trolls and bots have slowly turned Twitter into a political battlefield (4, 5).  However, the supreme strategic goal of such efforts may have been far more comprehensive than meddling in the U. S. 2016 election.  Evidence suggests Twitter trolls may have attempted to manipulate public discussions of contentious issues such as vaccination recommendations to inflame civil discord (4, 5).  Social media provide malevolent actors with opportunities to disseminate fake news, pollute and dilute legitimate content (5) and induce users to voluntarily segregate into almost tribal, self-reinforcing information bubbles (6).  These developments, dubbed “Truth Decay” (6) may produce environments where it is hard to establish even the most basic agreements.  Scientists confident clear and bold declarations of the facts will win the day may be in for a rude awakening.

Ask Not For Whom the Bot Trolls

NBC News published a substantial database of alleged (now deactivated) Twitter troll account tweets (7).  It is a downloadable Excel file which will allow you to find out what the trolls and bots were apparently interested in disseminating and insights into how they set about their tasks.  For example, a search of the terms ‘vaccine’ and ‘vaccination’ returned 98 hits while ‘scientists’ appeared in 117 data entries.  These keywords returned matches;  ‘cancer’ [200+], ‘Monsanto’ [51] and ‘genetic’ [19].  Try your own and look carefully, not all the tweets were obvious attacks or propagating false information.  

Prepare for Rapid Troll Evolution

Certain scientific research and medical interest topics have already been targeted by social media trolling operations.  The reason this is likely to continue is simple; some areas of research are controversial and stir deep emotions.  From the standpoint of those interested in stoking civil discord, such material could not be easier to exploit – simply post on social media and attempt to fan the flames. 

Digital warfare expert Clint Watts suggests the impressive impacts of troll farm operations on social media discussions have been duly noted by other organizations.  Accordingly, he predicts we should expect to see more methodical online trolling efforts originating from a wide variety of sources (8).  Scientists intending to conduct public outreach on social media may be well advised to investigate how known trolling operations currently work (9) and how to recognize if they are being targeted by systematic efforts to pollute content or worse (10).

Slippery slope

Who is following you?


The Extraordinary Threat of Predatory Journals

The rise of predatory journals willing to publish all submissions for a fee poses a grave threat to the scientific community research integrity.  Mimicking legitimate, peer-reviewed research journals, both scientists and the general public may have trouble distinguishing quality reports from more dubious or erroneous work.  Worse, pay-to-play sham journals are literally ripe for fraud and it may not be long before pseudo-scientists and social media content polluters recognize their potential.  Those seeking to sow discord may reap huge rewards by planting well-phrased tweets featuring links to bogus research publications and allowing confirmation bias to work its black magic.

The Cutting Edge Lagging Behind the Twitter Curve?

Scientists and corporations involved in genomic editing research and development face daunting challenges.  One of them is messaging.  Unlike their predecessors of not-so-long-ago, these talented men and women are under intense pressure to communicate with the general public.  A Twitter post paraphrasing some thoughts of professor of sociology Jenny Reardon (2) summarizes the situation neatly –

“Most people, scientists included, view it as a matter of determining which groups in society have access to beneficial technologies.  But there is also the question of which groups in society decide which technologies will be developed.” 

Genetics and Society (@C_G_S) Twitter post, 30 August 2018 

The corollary to this statement seems clear – communicate effectively with the public before someone else gets their message across. 

Who will exert the greatest influence on the development of new genome editing technologies?  In a time of information warfare the most ruthless entities with the most effective command of social media tactics may dictate the terms of our discussion. 

(1) Jon Turney.   Frankenstein’s Footsteps.  Science, Genetics and Popular Culture.  Yale University Press.

(2) Rick Mullin.   Building Bioethics into the Future of Life Sciences Innovation.  Chemical & Engineering News, 27 August 2018.

(3) Paul Berg.   Asilomar 1975: DNA Modification Secured. Nature 455:290-291.

(4) Jessica Glenza.   Russian Trolls ‘Spreading Discord” Over Vaccine Safety Online.  The Guardian, 23 August 2018.

(5) Jacqueline Howard.   Why Russian Trolls Stoked US Vaccine Debates.  CNN, 24 August 2018.

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

(7) NBC News database

(8) Clint Watts.   How Every Campaign Will Have a Troll Farm of its Own.  The Daily Beast, 9 April 2018.…

(9) Ben Nimmo.   #TrollTracker: How to Spot Russian Trolls., 29 March 2018.

(10) Clint Watts.   Messing With the Enemy.  HarperCollins.


The New Worry – Weaponized Incompetence

An essay by Rebecca L. Brown (1) makes the case that the strongest overall defense against acts of bioterrorism may be investing more resources in public health programs.  The logic is standard; active and effective public health surveillance systems may provide the earliest, critical first alarms and responses to deliberate attacks.  Since we have not seen a biological attack for quite a few years, the overall threat would appear to be low.  However, this paper reveals that this small number of successful attacks may be deceiving when it comes to accounting for the full spectrum of risks to the public from terrorist activities.


In addition to bioterror, it is also important to recognize the prospect of bio-error (2) in which accident or unforeseen circumstances result in releases of dangerous agents.  It is clear that nefarious actors have been/are pursuing biological warfare capabilities with mixed success.  Several reports suggest groups such as Aum Shinrikyo (1) suffered technical failures attempting to harness powerful biological agents.  In addition, the deaths of possible terrorists in Algeria due to an outbreak of plague were connected to alleged Al Qaeda efforts to produce biological weapons (3).

What Are the Chances?

We have instances of mishap and hints that disaster has befallen one group, but understanding the intentions and discovering the activities of secretive organizations limits risk estimates.  Are there any other ways to objectively assess the threats of bio-error?  We can examine some of the responses and records of the professional researchers (4, 5).  Accidents do occur, some have been serious and resulted in the loss of lives (4, 5, 6).  These calamities involved professional, well-trained researchers working in facilities at least initially deemed adequate to the tasks.  In the case of one experienced researcher working with an attenuated bacterium used in vaccine production, the precise sequence of events that led to his tragic death are unclear (6).  It seems probable that poorly trained personnel with inadequate equipment and in substandard facilities will suffer proportionately many more disasters.    


No Reassurance

Does technical incompetency offer reassurance that mal-intentioned groups will be unable to achieve their goal of large-scale bioterror attacks?  The requisite expertise to do some real harm can be acquired because, in part, the scientific community has yet to come to grips on how to control information on dual use technology research results.    In addition, the fundamental mindset of terrorist groups is hard to envision.  However, persons responsible for flying airplanes into buildings seem unlikely to have much concern about escape of bioterror agents into surrounding communities or the fate of those assigned to work with dangerous agents.  Clearly, any proliferation of groups pursuing bioterror ratchets up the risk of bio-error events.  Unfortunately, the central goal of sowing disease and fear may be achieved whether a disaster is unleashed deliberately or incompetently.      

(1) Rebecca L. Brown.   Bioterrorism: Fear Accidents More than Attacks.  Bulletin of the Atomic Scientists, 29 August 2018.

(2) C. Stevenson. 2016.  Keeping Biosecurity in the Forefront: A Conversation with Renee Wegrzyn.  Synbiobeta, 28 December 2016.

(3) Anonymous.  2009.  Al-Qaeda Cell Killed by Black Death ‘Was Developing Biological Weapons.’ The Telegraph, 20 January 2009.

(4) Richard Van Noorden.   Safety Survey Reveals Lab Risks.  Nature, 2 January 2013.

(5) Martin Furmanski.   Threatened Pandemics and Laboratory Escapes: Self-fulfilling Prophecies.  Bulletin of the Atomic Scientists, 31 March 2014.

(6) Emma Graves Fitzsimmons.   Researcher Had Bacteria for Plague at His Death.  The New York Times, 21 September 2009.


Can’t Quit You, Smallpox

Smallpox killed its last victim almost exactly 40 years ago.  Two years later the disease was declared officially eradicated.  Although the chain of natural transmission was effectively broken decades ago, the disease remains a concern to medicine (1).  Drawing attention to the recent U. S. Food and Drug Administration (FDA) approval for a drug treatment (1), an editorial published in Nature makes the case for continuing efforts to control or prevent smallpox.  The reason is simple; no one can be certain the often deadly disease has claimed its final victims.


Smallpox virus

The Known Risks

Smallpox is eradicated, but is not truly extinct since viable stocks of the virus are being maintained in special facilities in the U. S. and Russia.  Noting these conserved samples are essential for research and worried about possibilities the disease might return, officials have declined – repeatedly – to destroy them (1).  The irony is that although maintaining virus stocks is deemed an essential public health safeguard, laboratory mishaps are a proven method for smallpox escape (1, 2).      

Recounting the tragic story of medical photographer Janet Parker who was working at the Birmingham Medical School when she became infected with the smallpox virus, the Nature editors point out that her death was ascribed to laboratory mishap (1).  Retrospective investigation revealed that faulty practices and ventilation allowed the virus to drift where she had been working one floor above the smallpox lab (1, 2).  From 1963-1978, escapes from two separate, accredited labs in Great Britain resulted in 80 total smallpox cases with 3 fatalities (2).  The fact that highly pathogenic agents have been released from biocontainment facilities (2) underscores the fact that maintaining smallpox stores in labs carries some, hopefully minimal, intrinsic risks.                     

The Potential Risks

Smallpox virus stocks have been used and stored over the years in multiple facilities.  A surprising discovery of forgotten stored virus at the U. S. National Institutes of Health (NIH) reveals record keeping may have been lax and it may not be safe to assume all samples have been destroyed.  In addition, the virus was weaponized at least once and viable stocks could still be held under the auspices of clandestine programs (1).  Whether smallpox virus is re-introduced to the world through mishap or malice as a consequence of sanctioned work, terrorist plot or the actions of a single, perhaps demented, individual the outcome could be catastrophic.

A Look-Up and Cook-Up Future?

The emergence of synthetic biology provides a potent rationale for continuing robust efforts to prevent and treat smallpox.  What were near-impossible fantasies about synthesizing viruses 15 years ago are racing toward routine implementation today.  What miracles – and potential nightmares – will this fast-unfolding future bring us?  Unfortunately, it could be a future where some genetic information itself poses a potential threat.  One worry is that advances in the power and ease-of-use of new synthetic biology technologies may make it feasible for a person(s) unknown to take the already published smallpox genomic sequence information and use it as the recipe to cook up their own virus masterpiece.                     

But, Have We Gotten the Full Story?

There is something baffling about the smallpox story.  Why have the authorities been so reluctant to destroy the last known stocks of this virus?  Assuming for the moment that the U.S. and Russian caretakers could devise a way to assure their counterparts had complied faithfully and fully with orders, why hold on to this threat?  Even if there are other virus stocks hidden away someplace, the smallpox virus itself is not necessary to conduct drug trials (1).  In fact, smallpox virus is not needed to produce vaccines either.  The modern vaccination process initiated and publicized by Edward Jenner (3), uses a relative that produces minor disease, cowpox (vaccinia) virus, to induce solid immunity to the far more dangerous smallpox (variola) virus.  The immunization process employed today is basically the same as that Jenner used two centuries ago (4).  As long as we have cowpox, we could make vaccines that would protect us against natural smallpox.    

cowpox and needle

For the moment, for a variety of reasons, the persons in charge continue to maintain smallpox virus stocks.  The risks posed by that decision are currently extremely low.  In addition, vaccine stocks are in hand and new drugs are being developed.  However, other than the fact that we will never be able to forget smallpox completely, we have only vague notions of what the future might bring.   


(1) The Editorial Board.   The Spectre of Smallpox Lingers.  Nature 13 August 2018.

(2) Martin Furmanski.   Threatened Pandemics and Laboratory Escapes: Self-fulfilling Prophecies.  Bulletin of the Atomic Scientists, 31 March 2014.

(3) Greer Williams.  1959.   The Virus Hunters.  Knopf.

(4) The Centers for Disease Control and Prevention.


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