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Publishing the CRISPR Twins Research – Understanding the Audiences

An announcement that twins modified using CRISPR genetic editing had been born unleashed an immediate wave of condemnation from scientists.  With that event comes the big question – now what?  Much hinges on the scientific community answer.

Megan Molteni examined questions swirling around future formal publication of these experiments on human embryos (1).  One rationale to go forward with publication is utilitarian; the technical information might be useful to others in the future.  However, a strong counterargument is that allowing publication in the scientific literature rewards the blatantly unethical actions of a rogue.  The scientific community has grappled with the proper disposition of research results obtained through unethical practices since before the time of the Nuremberg trials.  Utterly shameful doings are one thing, are scientists managing to avoid the slippery slope when violations are not so obvious?

Slippery slope2

Whataboutism and a Focus on Technical Details

An article published in The New York Times (2) pointed out how the birth of CRISPR babies is not all that ground-breaking in one sense.  Genetically modified human beings, produced by different mechanisms than CRISPR, already exist.  An interesting facet of this story is that one of the seminal works (2), the birth of a 3-parent baby, sparked its share of controversy (3).  Stymied by F.D.A. regulations, this ambitious mitochondrial replacement therapy researcher relocated the project to a country admittedly selected because it lacked restrictive rules (3) and the results have been published in the scientific literature.  Perhaps that would not have happened if the experiment had been a tragic failure.  But could apparent success and the fact that genetically modified babies are technically old news make it easier to rationalize publishing the full details of the new CRISPR babies work?

No Harm, No Foul?

Unfortunately, medical research sometimes exposes human participants to hazards.  Investigators are required to inform subjects of the risks and potential adverse events as fully as possible.  In addition, scientists are expected to take actions to mitigate foreseeable problems.  Safeguarding the health and wellbeing of the research subjects is paramount, the needs of the investigators are secondary considerations.

Meticulous preparation prior to undertaking clinical trials is no guarantee the efforts will proceed as investigators hoped.  A trial of a promising drug candidate to combat Alzheimer’s disease (AD) had to be terminated after unanticipated, serious adverse events were observed (4).  Once the problems were recognized, the study was ended immediately.

As far as anyone knows the CRISPR twins are fine.  So, no harm, no foul?  If investigators have been permitted to publish in a high-profile journal the details of a failed drug trial that seriously injured many participants (4), why are there so many questions over doing that with the CRISPR babies data?  In one sense accounting for the difference in peer/community reaction is simple; the AD trial was conducted in an ethical manner and the welfare of the participants took priority over all other concerns.  The contrast with the work put forth by an apparently over-ambitious and unethical rogue could not be more stark.

vermeer

One general issue with the 3-parent and CRISPR babies is no one will know with certainty whether or not the manipulations produced any adverse impacts for quite some time in the future (3, 5).  In the earliest public discussions of CRISPR genome editing, Nobel laureate David Baltimore suggested that a fundamental lack of knowledge regarding consequential impacts of alterations should discourage such efforts in humans for the time being (6).  The true potential tragedy of the CRISPR babies is that the news reports lead us to conclude there was no compelling medical need to perform the experiment.  A driven investigator may have secured his place in scientific history, but only the passage of time will reveal how much that achievement might ultimately cost the CRISPR babies. 

To Expunge or Not to Expunge?

The article by Molteni (1) points out that refusing to allow the CRISPR babies study to be published poses another dilemma.  She reminds us that publication serves two purposes, career building and knowledge accrual, leading to a concern that preventing the work from entering the written official record effectively throws away knowledge.  The scientific community has been grappling with the holes-in-the-official-record problem posed by failed – and therefore unpublished – clinical trials funded by private corporations.  Predicated on solid rationales that others might invoke as well, clinical trial data and approaches which did not achieve desired endpoints are still vitally important to future investigators because they may help prevent effort being wasted running down blind alleys that have already been traveled.  There are at least two ways to look at the CRISPR data publication dilemma – the study, or at least the manuscript describing it, is being characterized as “shoddy” (1), so its absence from the scientific record may not be a huge loss.  However, it might serve as an example of what not to do for future researchers, provided a person with demonstrated contempt for ethics deigns to convey his work and results truthfully.  Should a manuscript of suitable quality ever be produced, perhaps this would be a moment for a publisher to accept the work with the condition that a critique will appear alongside it.                     

Facing the Court of Public Opinion

It is important to recognize the current rules and guidelines for research involving human subjects have been refined over a period of decades and after some hard lessons.  And it seems true that now-notorious projects conducted in the past such as the Tuskegee study and Operation Sea-Spray (1) would probably never receive peer approval today.  We may take some comfort in that, but the legacy of prior transgressions still hangs over us.  The common thread between the work performed at Tuskegee and for Operation Sea-Spray was the deliberate use of human beings in an instrumental fashion to accomplish the goals of the scientists.  To anyone who maintains those days are long gone, take another look at the CRISPR babies story. 

Editing of the human germline will probably be done somewhere.  However, the work can – and must – be performed transparently and ethically, which will qualify it for publication in the scientific literature.  Citizens might not be interested in the deep technical details of this research, but will certainly comprehend what a mess the CRISPR babies debacle has exposed.  And they will definitely understand what it means if a utilitarian rationale is employed to justify the decision to publish such derivative, thoroughly unethical and probably substandard work. 

At this stage the most important audience for genome editing scientists is not their fellow research journal-reading colleagues, but the ordinary citizens who comprise the court of public opinion.  

Balance       

 

(1) Megan Molteni.   How Do You Publish the Work of a Scientific Villain?  Wired.com, 11 December 2018.  https://www.wired.com/story/how-do-you-publish-the-work-of-a-scientific-villain/

(2) Carl Zimmer.   Genetically Modified People Are Walking Among Us.  The New York Times, 1 December 2018.  https://www.nytimes.com/2018/12/01/sunday-review/crispr-china-babies-gene-editing.html

(3) Sara Reardon. ‘Three-Parent Baby’ Claim Raises Hopes – and Ethical Concerns.  Nature, 28 September 2016.  https://www.nature.com/news/three-parent-baby-claim-raises-hopes-and-ethical-concerns-1.20698

(4) Rachelle S. Doody et al.   A Phase 3 Trial of Semagacestat for Treatment of Alzheimer’s disease.  The New England Journal of Medicine, 25 July 2013.     https://www.nejm.org/doi/full/10.1056/NEJMoa1210951

(5) David Cyranoski.   Baby Gene Edits Could Affect a Range of Traits.  Nature, 12 December 2018.  https://www.nature.com/articles/d41586-018-07713-2

(6) Nicholas Wade.   Scientists Seek Ban on Method of Editing the Human Genome.  The New York Times, 19 March 2015.   https://www.nytimes.com/2015/03/20/science/biologists-call-for-halt-to-gene-editing-technique-in-humans.html

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Winter is Coming – A Message From the Vanishing Insects

 

Agreeing to write a brief profile of an endangered species for a wildlife group, I searched for information about an obscure Arizona insect known as the Stephan’s riffle beetle.   One of the first items uncovered – almost 2 years ago the U.S. Fish & Wildlife Service had declared this species probably extinct which made it ineligible for protection under the Endangered Species Act.  However, biologists will continue to monitor locations once known to harbor these tiny (0.1 inch) beetles (1). 

Stephans riffle beetle

The Stephan’s riffle beetle was at high risk for extinction because it inhabited such a tiny geographic area; a couple of Madera Canyon springs in the Coronado National Forest of Arizona.  These beetles spent most of their lives in the water, including the adult stage.  Requiring high dissolved oxygen levels, they were confined to quick-moving, clean streams.  Unable to fly or migrate long distances, any situations such as drought or fire causing a reduction and warming of water flows posed an imminent threat to their survival (1).         

The lesson in all this is that a decline in the abundance of a species may be brought about in many ways; habitat loss, environmental pollution, climate change or a combination of factors.  Whatever the cause(s), shrinking numbers may leave survivors in smaller, more isolated regions with a corresponding elevated risk of extirpation due to simple ecological happenstance such as drought or unseasonable weather. 

The Stephan’s riffle beetle had been balanced on the knife edge of extinction since it was first described in 1969 (1).  While the loss of such an obscure creature will be mourned by few, now come reports that a shockingly high number of insect species seem to be in precipitous decline (2).  Although most of us probably have not noted anything amiss and can only name a few ‘bugs,’ the emerging information suggests formerly abundant insect life – a critical component of natural food webs – is vanishing before our eyes.  If we are witnessing a global-scale insect defaunation (2), the ecological ramifications are staggering.  The insects will not go alone.     

Sort of Seen It Before

The few documented declines of the insects have been so gradual and involved such small and seemingly insignificant creatures, they proceeded largely unnoticed.  So far, the full extent of the losses remains uncertain as are the factors behind them.  It is possible that the causes may be different for each location, although some investigators favor the notion that the best candidate to explain the observations is a steadily warming climate (3).

The closest familiar analogue of a large-scale insect defaunation for many of us could be the normal changes we see annually as the Summer slowly turns to Fall.  With the frosts, some insects die in the field or hibernate and during the pleasant Indian summer days you might have noticed the near absence of annoying mosquitoes, flies or ants.  The future might be a bit like that except our missing co-inhabitants never return with the Spring and a world once abuzz with life becomes unfriendly.   

Long live the Stephan’s Riffle Beetle.  Soon we may understand your message all too well.

Dead wood

(1) U.S. Fish & Wildlife Service. 2016.  Southern Arizona’s Stephan’s Riffle Beetle Believed Extinct.  Press Release, 5 October 2016.  https://www.fws.gov/news/ShowNews.cfm?ref=southern-arizona%E2%80%99s-stephan%E2%80%99s-riffle-beetle-believed-extinct-&_ID=35838

(2) Brooke Jarvis.   The Insect Apocalypse is Here.  The New York Times, 27 November 2018.  https://nyti.ms/2DMT70v

(3) Karen Weintraub.   Male Insect Fertility Plummets After Heat Waves.  The New York Times, 13 November 2018.  https://www.nytimes.com/2018/11/13/science/sperm-infertility-insects-heat.html

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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.

__________________________________________________________________________________

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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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.   

SA

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.

IMG_3883

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.  ProPublica.org, 10 October 2017.  https://t.co/r9PZ6dph0i

(3) Maria Angeles Argudin et al.   Food Poisoning and Staphylococcus Enterotoxins.  Toxins 2(7):1751-1773.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153270/

(4) Centers for Disease Control and Prevention. Staphylococcal (Staph) Food Poisoning. https://www.cdc.gov/foodsafety/diseases/staphylococcal.html

(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.   http://journals.sagepub.com/doi/pdf/10.1177/153567600601100303

(6) Bettina C. Fries and Avanish K. Varshney.   2013.  Bacterial Toxins – Staphylococcal Enterotoxin B.  Microbiology Spectrum 1(2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086421/

(7) Gabrielle Tarini.   2016.  Keeping the Biological Weapons Convention Relevant.  Bulletin of the Atomic Scientists, 1 November 2016.  https://thebulletin.org/2016/11/keeping-the-biological-weapons-convention-relevant/

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

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‘Bye, Jupiter? The Ethics of Space Exploration

 

Benjamin Sachs (1) and his colleagues at the University of St. Andrews (2) are working to create a framework for extraterrestrial environmental ethics.  What deep philosophical questions could possibly be raised by space exploration you ask?  The basic approach toward outer space discovery and demonstration projects is about to change.  Once the exclusive realm of a few nation-states, a combination of advancing technology and private enterprise is literally democratizing space.  Poised to have a new wave of explorers and devices fan out in the solar system, some swift introspection is essential.

It’s Always All About Us

Is there any value to the Universe beyond human needs and desires?  Do we afford special consideration to any living entities we discover?  What if the living things we find are ‘only’ microbes? 

To date great efforts have been undertaken to prevent inadvertent forward contamination of Mars and other solar system sites with terrestrial microbes.  This reflects the fact that scientific curiosity has been a significant impetus for exploring solar system bodies.  Avoiding contamination reflects a basic exigency for life detection missions – scientists are interested in discovering novel, indigenous microbes, not terrestrial hitchhikers or invaders.

Finding unique life forms on Mars or other solar system sites, confirming a ‘second genesis’ took place, would be a tremendously significant scientific discovery and undoubtedly stimulate a large number of follow-up studies.  Then what?  Is there a moral duty to preserve such ecosystems?  Would discovering living residents make Mars permanently off limits for ‘terra-forming’ proposals?

If private enterprises begin to dominate space exploration, we may have to contend with situations in which the needs of the corporation do not coincide with those of the scientific community or governments.  Would a company be willing to face restrictions on terra-forming operations to keep some silly bacteria on Mars alive?  Would corporate attorneys argue that the Tellico Dam-snail darter precedent (3) applies to Mars?  In that case, since the company has already embarked on its vision of the 21st Century resurrection of Manifest Destiny, the prior claims of any lowly Aresian microbes would be void.  Hopefully, the failed litigants will find the new and improved Martian world to their liking.  If not, perhaps terra-forming companies will underwrite programs to preserve the genetic materials of the endangered species, selling it as a conscience-soothing hedge against extinction.

But, ‘No’ May Not Last Forever

Whether or not we agree humans have a moral duty to preserve planetary and other solar system environments, there is a scientific rationale to ensure such efforts are in place.  Technology changes. New knowledge accretes and capabilities expand.  The Viking lander missions to Mars in the 1970s are a prime illustration.  Those landers were marvels of engineering for their day and they conducted direct tests to demonstrate the presence of living organisms in samples of Martian soil.  Today, using molecular probes and technologies that did not exist in 1976, scientists have capacities to detect microorganisms that cannot be cultured.  A search for life using molecular tools would likely yield quite different results from those where investigators could only study organisms that were active under the culture/incubation conditions the engineers guessed would be both good and practical to achieve.  In short, a sample confidently declared ‘dead’ in 1976 might return a different result if it was checked with the more powerful, culture-independent methods in use now.  Like archaeologists leaving portions of known sites unexcavated to await future investigators with new tools, perhaps planetary scientists will note that emerging technologies could yield new insights and take steps to safeguard pristine samples.  Perhaps the official rule-makers will mandate a go-slow approach to space body development strategies.          

Leave No Trace in Outer Space?

Sachs also wonders if humans are under an obligation to preserve the physical environments of the worlds we will explore (1).  If a body is declared (probably) dead are we then totally free to plunder it?  In the case of potentially resource-rich asteroids, will profit-making entities be allowed to literally consume them?  Should some places be deemed common heritage sites off-limits to all but the most careful expeditions?  That might be a very tough sell.

The Apollo mission lunar landing sites unintentionally illustrate a ‘leave no trace’ ethic has not been embraced by NASA Moon explorers.  Environmental conditions on the Moon will enable these artifacts of exploration to endure far into the future.  Some thoughts have been given to ensuring historic areas like these on the Moon are protected against damage or looting by future tourists (4).  While getting a selfie standing next to a flag planted by 20th century astronauts may seem like a great idea, tourist traffic might quickly obliterate the authentic footprints of the original explorers.  However, toxic dust (5) may mean large parts of the Moon will turn out to be not so hospitable to tourists and thereby prevent lunar heritage sites from being overrun.  Other locations may also remain pristine because they are simply too unpleasant for humans. 

Moon base

Changing Situations

Will the democratization of space exploration lead to anarchy?  It is not clear what changes the forces of private enterprise will produce.  Where will authority to permit or deny proposed activities be vested?  Perhaps we are entering an age with millionaires on the Moon, tycoons sovereign on Titan and plutocrats presiding over Pluto.  For those of us ordinary citizens with dreams of space exploration, the significance of moneyed interests enables us to make one solid prediction –

No matter where you go, there’s your landlord.   

Bye Jupiter  

 

(1) Benjamin Sachs.   Eight Questions We Should Ask About the Ethics of Space Exploration.  The Conversation, 27 June 2018.  https://qz.com/1316782/is-space-exploration-worth-the-ethical-cost-eight-questions-we-should-ask/

(2) University of St. Andrews, Centre for Ethics, Philosophy and Public Affairs – Exoplanet Ethics. http://ceppa.wp.st-andrews.ac.uk/research-projects/exoplanet-ethics/

(3) Teresa Sparks. TVA and the Snail Darters: A Case Study in Environmental Managementhttp://web2.utc.edu/~John-Tucker/Courses/esc430/esc430mat/darter/tellico.html

(4) Daily Mail Reporter.   Look, but Don’t Touch!  NASA Releases Set of Guidelines for Potential “Moon Tourists” to Preserve Apollo Landing Sites.  Daily Mail, 7 November 2011.    http://www.dailymail.co.uk/sciencetech/article-2058614/Moon-tourists-given-guidelines-Nasa-bid-preserve-Apollo-landing-sites.html

(5) The Toxic Side of the Moon.  2018.  ESA, 4 July 2018.  http://www.esa.int/Our_Activities/Human_Spaceflight/The_toxic_side_of_the_Moon

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Unpredictable Outcomes – Percival Lowell, Clyde Tombaugh and the Discovery of Pluto

I visited the Lowell Observatory (1) at Flagstaff, Arizona, on June 29, 2018.  Now a National Registered Historic Landmark on Mars Hill just west of old Route 66, the Observatory was founded in 1894 by Percival Lowell.  Its primary mission was to study the planets of the solar system with Mars being a particular focus of attention.  We arrived just in time to take The Story of Pluto Guided Tour which culminates in the Lawrence Lowell Telescope building.  This is the site of discovery of Pluto and houses the astrograph and guide telescope actually used by Clyde Tombaugh in that effort.

Astrograph

The Lawrence Lowell Telescope building where Clyde Tombaugh discovered Pluto

Our tour guide gave us a lively overview of the observations that prompted a systematic search for an unseen ‘Planet X’ as Percival Lowell had designated it.  Along with the scientific aspects some history of the interesting characters in the story was provided.

The astrograph was a home-brew affair, built to handle the challenging conditions of wind and weather of Mars Hill.  The 13-inch (33 cm) objective optics features a unique triple lens arrangement designed to enable large format plates (photographs) to be exposed.  Stanley Sykes and his son Guy constructed the double-anchor point mount and a local carpenter (Mr. Mills) built the dome (2).  Clyde Tombaugh, a young man with no formal academic credentials at that time was hired to conduct the arduous search.  One of his first jobs to was to finish and paint the new astrograph (2).  Although it now sports a shiny metallic gray color, it was once (Mars?) red. 

Astrog and guide

The Lawrence Lowell astrograph and guide telescope used by Clyde Tombaugh

The Path To Pluto Via Mars

Pluto walk

An intense fascination with the planet Mars led Percival Lowell to found the Observatory that still bears his name over a century later.  Influenced by the writings of astronomers Giovanni Schiaparelli and Camille Flammarion (3), Lowell initiated his own studies of Mars and promoted the hypotheses that this world harbored a living, active biosphere inhabited by intelligent beings (3).

Mars (2)

In his lectures, articles and books, Lowell explained how his observations of artificial canals on Mars revealed the story of a drying planet and a civilization responding with an engineering effort of gigantic scale (4).  The goings-on of the times were probably inescapable influences and several contemporaneous, large-scale canal construction projects had naturally drawn public attention in Lowell’s day.  The War of the Worlds was published a few years after Lowell began his observations and that circumstance coupled with the fact the location names employed by Giovanni Schiaparelli on his Mars maps were evocative and included linear features designated ‘canali’ (3) might have all combined to channel his thinking.

Lowell’s public lectures and 1908 book, Mars as the Abode of Life (4), ignited public interest.  His story – based on personal observations made with one of the finest telescopes in the world at that time – was compelling and it made him famous.  As a young man with a deep interest in astronomy, Clyde Tombaugh was well acquainted with the ideas of Percival Lowell and considered him a personal hero (2).  When Tombaugh sought professional advice on the planetary observations he was making with his hand-built telescope, he wrote to the Lowell Observatory.  That decision, perhaps based on perceived kinship with the late Percival Lowell, ultimately changed his life and the institution forever.  Tombaugh had no academic training, but possessed a deep love of astronomy along with a meticulous approach to work that enabled him to succeed in the grueling quest to locate Planet X predicted by the calculations of Percival Lowell.  Absent Clyde Tombaugh the discovery of the first trans-Neptunian object might have been long delayed (2, 5) and may not necessarily have occurred at the Lowell Observatory.

The Road to Redemption

Lowell extrapolated his observations of Mars surface features into evidence for an advanced civilization coping with adverse changes in planetary climate.  Further, he deduced the existence of a global canal system revealed the Aresian political environment was fundamentally different from that of Earth; the Martian engineers obviously believed in cooperation (4).     

Percival Lowell already possessed a personal fortune, so he had no financial motive to indulge the fantasies of any audience in order to sell books or pamphlets.  The Mars narrative he championed reflected personal beliefs and it made him – as well as his institution – pariahs to many in the professional scientific community (2).  A letter published in the journal Science (6) states the issues explicitly.  Lowell was accused of feeding pseudo-science to a naïve, but enthusiastic, public.  Noting Lowell’s impressive ability to communicate with the general public, the errors, misrepresentation of theories as established fact and lack of supporting data were judged worthy of censure.  Allowing that Lowell was discussing his own observations and that it is his privilege to interpret them as he saw fit, the letter author still concluded his actions were deceptive and “immoral.”

Clyde Tombaugh had the opportunity to observe Mars using the same 24-inch telescope once employed by Lowell.  Noting that he saw and drew lines like those of Lowell (5), Tombaugh pointed out that many critics were not actually planetary observers.  Despite his personal experiences and admiration of Lowell, Tombaugh recognized the realities of the canals of Mars (2, 5). 

With so much of the scientific community hostile, Percival Lowell and the Observatory staff were ‘outcasts’ (2).  When Clyde Tombaugh arrived at the Observatory over a decade after Lowell’s sudden death, the astronomers were still demoralized due to their ‘ostracism’ (2). Recognizing the discovery of a new planet would be heralded and draw immediate competition, Lowell Observatory managed their formal announcement carefully, well aware of their ‘underdog’ status (5) and the opportunity for professional reputation redemption it would provide. 

It is hard to imagine the acclaim and prestige such a discovery would bring.  Possibly one of the finest actions ever taken by the Lowell Observatory staff and leaders was the decision to give Clyde Tombaugh – the young man without formal training – full credit for his essential contributions to the successful team effort to find Planet X.  Who discovered Pluto?  To this day most of us answer ‘Clyde Tombaugh,’ although I bet he would probably have pointed out the journey began with Percival Lowell’s mathematical calculations and the work of observatory staff long before he arrived.

The Unpredictable

It is recognized that the discovery of Pluto based on Percival Lowell’s mathematical predictions for an unseen Planet X was sheer coincidence.  Almost immediately the Lowell Observatory staff and others were concerned that the estimated mass of Pluto was too small to be the cause of the perturbations in the orbits of Uranus and Neptune that launched the effort.  During the Story of Pluto Guided Tour, our presenter noted how the astronomical symbol for Pluto, could be interpreted as Percival Lowell’s initials or, more fancifully, as an enshrinement of “Pretty Darn Lucky.”  

 Hubrids 2

Driven by his personal interests, Percival Lowell carved out his place in the pantheon of astronomy.  Vilified by the scientific community of his time, Lowell and his ideas became famous among the general public.  Clyde Tombaugh considered him a personal hero.  Could it be that the discovery of Pluto was initially set in motion when Clyde started reading the writings of Lowell and emulating him?

Could works today decried loudly as pseudoscience such as The UFO Hunters program or efforts to find Bigfoot actually be seeding the next generation of scientists?  This is not a plea for skeptics to cease their critiques, I believe firmly they must continue their work, point out fallacies and show how a scientist might approach the issues.  But perhaps we will allow that some of us, possibly many of us, first start out like Percival Lowell and Clyde Tombaugh with nothing more than an intrinsic deep interest in a topic.  The scientific expertise (hopefully) will develop later.  A quote attributed to Ray Bradbury (3) sums it up –

“It’s part of the nature of man to start with romance and build to reality.” 

The evidence suggests professional astronomer peers held the work of Percival Lowell in generally low esteem.  The passage of time has revealed his overall claims regarding the planet Mars were indisputably untrue.  Still, they might have captured the imagination of the young Clyde Tombaugh and set the stage for him to make some amazing discoveries.

(1) The Lowell Observatory. https://lowell.edu/

(2) Clyde W. Tombaugh and Patrick Moore.   Out of the Darkness.  The Planet Pluto.  Mentor Books.

(3) William Sheehan and Stephen James O’Meara.   Mars.  The Lure of the Red Planet.  Prometheus Books.

(4) Percival Lowell.   Mars as the Abode of Life.  Reprinted (2000) by Bohn Press.

(5) David H. Levy.   Clyde Tombaugh. Discoverer of Planet Pluto.  Sky Publishing Corporation.

(6) Eliot Blackwelder.   Letters – Discussion and Correspondence – Mars As The Abode of LifeScience 29:659-661, 23 April 1909. http://science.sciencemag.org/content/29/747/659

For younger readers –

Tony Simon.  1965.  The Search for Planet X.  Scholastic Book Services.

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CRISPR At-Home Diagnostics – The Questions to Come

Move over, biohackers.  A biotech company has plans to put CRISPR technology into the homes of consumers for DIY medical diagnosis (1).  “Dr. Google” and WebMD, take note, CRISPR-based diagnostic tests may make you obsolete (1).

CRISPR, the Ultimate Diagnostician

CRISPR technology has drawn attention primarily because it enables the precision alteration of genomes.  However, the capacity to locate specific nucleic acid sequences also means it could seek out and reveal viruses and other invaders.  Highly specific, potentially able to allow fast, sensitive and unambiguous identification of pathogens that are difficult or dangerous to culture, CRISPR technology might be the future of infectious disease diagnosis.  Can the amazing capacities of CRISPR be translated into at-home diagnostic tests?      

The Sharpest Double-Edged Sword

The article (1) mentioned malaria and Zika virus as potential CRISPR-based diagnosis targets.  Zika virus infection is an emerging global concern posing particular risks during pregnancy (2, 3).  In general, Zika virus and its close arbovirus relatives are difficult to culture and diagnosing illnesses caused by them is challenging in the earliest stages.  Assuming the technology lives up to its potential, the speed, sensitivity and specificity offered by a validated CRISPR test method might be a huge advance.  How might an at-home test for Zika virus infection perform in the real world? 

Because of its potential to produce devastating birth defects and Guillain-Barré syndrome, concern about Zika virus infection is warranted.  And the virus is sneaky; a majority of infected persons, possibly up to 80% (2), never exhibit signs or symptoms of infection.  Zika virus is transmitted by mosquito bite, but it can also be passed by sexual contact months after initial exposure.  The Centers for Disease Control and Prevention (CDC) has criterion-based recommendations for Zika virus testing (3).  Current nucleic acid-based tests are effective only for about 2 weeks after onset of symptoms.  After that point the virus is typically cleared from circulation and clinicians will then rely on tests that reveal patient antibodies.  Again, most patients never show any signs or have any symptoms after being infected with Zika virus.

A Future Scenario

A male traveler spent time in an area where Zika virus was circulating.  Immediately after returning home, he and his wife decided they would like to start a family.  However, he knows it is possible to transmit Zika virus to his wife through sexual relations for up to 6 months after infection.  A validated at-home Zika virus CRISPR infection blood test kit is available and he used it.  The test was negative for Zika virus.

Is he OK to try to start a family immediately or is he better off waiting for 6 months?

The DIY Passage to the Future

Here are some questions that impact the decision – did he ever have any signs (rash, fever) or symptoms (feeling unwell, muscle aches) that might indicate Zika virus infection?  When did he have them and when did he perform the DIY Zika virus test?  Timing is everything here because if the new CRISPR diagnostic test uses blood it will probably have a limited reliable detection window just like the current nucleic acid tests. Perhaps the coming CRISPR at-home Zika virus test system will be extremely sophisticated and combine nucleic acid surveillance with antibody screens.  Hopefully, the at-home kits will include information to enable users to understand how the procedure(s) works, explain that under some circumstances the different formats return apparently contradictory findings and point out critical limitations that impact final interpretation of results.  Again, if you look at the CDC guidelines for Zika virus testing (3) you will see how and when to apply them involves several factors.  So, back to the scenario; are you ready to make the call?  What if it was your baby on the line?   

Janus2

 

Maybe the future for a case like this one lies in methods able to assess semen samples which could give patients the most accurate sense of risk for Zika virus transmission through sexual contact.  Even the most powerful tests will have limitations and it will be interesting to see how Mammoth Biosciences and others approach the CRISPR diagnostics at-home market.  If the “internet makes us freak out about our health” (1) imagine what is going to happen when a diverse population of consumers are empowered with their own personal medical testing capabilities.   

 

(1) Kristen Houser. At-Home CRISPR Kit Will Diagnose You Better Than WebMD.  Futurism, 27 April 2018.  ly/2MRf4O6

(2) Shamez N. Ladhani et al.   Outbreak of Zika Virus in the Americas and the Association with Microcephaly, Congenital Malformations and Guillain-Barré Syndrome.  Archives of Disease in Childhood 101(7):600-602.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941169/

(3) Centers for Disease Control and Prevention. Testing Guidance for Zika Virus.  https://www.cdc.gov/zika/hc-providers/testing-guidance.html \

(4) Centers for Disease Control and Prevention. Men and Zika. https://www.cdc.gov/zika/men/index.html

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A Wild Ride Comes to an End

June 22, 2018

In a few days I will wrap up my final set of experiments.  Having been engaged in research nearly 40 years this is a big personal milestone.    

It’s been quite a journey.  From restriction mapping the DNA of human tumor virus BK, cloning the recA gene analogue of Pseudomonas aeruginosa, hunting bacteriophages to using hard-core biochemistry to examine Alzheimer’s disease, it was never boring.  I have always had a great deal of good luck in my life and at each step along my path I discovered helpful mentors and good colleagues. 

I have included a few waypoint pictures.  Not everything resulted in publications indexed on PubMed.  Truth be told, some of the more interesting projects involved what is loosely termed the paranormal – UFO’s, cryptids, alien abductions, etc.  Are such efforts beneath the dignity of true scientists?  It depends on the scientists.  However, I am able to report that along these often ridiculed trails I met some fascinating people, had tremendous amounts of fun and learned more than I ever dreamed possible.

Being able to live this life has been a privilege.

 

Tangles

Tau tangles in the neurons of an AD patient

 

cyclops1

A red Cyclops from an alkaline lake

 

dinobone

Dinosaur bone

 

UFO

UFO Hoax

 

UNL1

UNL-1, a bacteriophage with a novel UV damage reactivation phenotype

 

OLYMPUS DIGITAL CAMERA  OLYMPUS DIGITAL CAMERA

The Triassic Trees of Dobell Ranch

June 13, 2018

If you have seen a petrified wood specimen featuring bright red, purple, orange-yellow colors, chances are good it came from Northeast Arizona.  Petrified wood may be found in many locations, but only a few spots produce specimens with such vibrant colors.  Larry Jensen and I visited the Dobell Ranch dig site located near Holbrook, Arizona, to find out how the petrified wood samples we have seen in rock shops and shows are collected.  The picture below of a polished petrified wood cross-section table top was taken at the Tucson Fossil and Gem Show.

Pet wood table

Rhonda Dobell runs a curio shop not far from what is probably the petrified wood capitol of the world, Holbrook, Arizona.  I am not sure how long she has been excavating and selling petrified wood from this land, but was informed the ranch has been held by the Dobell family since 1932.  A sizeable selection is available for customers at her roadside curio stand and the active dig site is nearby (an easy drive) with a lot more items of every size.

Pick and choose

 Part of the offerings at the Dobell Dig Site

What she sells is the real deal; petrified wood cleaned of dirt and extraneous deposits of debris in an otherwise unmodified state.  In some instances the gross external morphological features were so well preserved it is hard to believe that you are not looking at a tree.  To convince yourself, simply try picking up one of them.  Or take a look at the Big Sky country around you and imagine where you have to trek in these parts to get such a thing.

Waiting

Rhonda’s granddaughter waits for some work

The petrified wood is excavated from a deep, soft overburden.  These logs dating from the Triassic period (ca. 200 million years ago) were apparently buried quickly in sediments and volcanic ash and then fossilized/colored by quartz and other minerals.  Quite a bit of the original matrix complete with what look like polished river rocks surrounds the petrified wood. 

Dobell dig

I am not sure how deep the covering deposits run, but pits I estimated to be up to 30 feet deep were being worked at the time of our visit.  Pictured below is a log in the excavation process. Rhonda pointed out another log lies directly beneath.  A photograph from a different vantage point with Rhonda’s granddaughter provides some perspective.

Excavation  Perspective

An interesting feature of some of the petrified logs was that the fossilization process sometimes preserved hollows and voids, some retaining signs of apparent termite damage.  For the giant undergoing excavation, Rhonda showed us exactly where she knows (through tapping) a hollow area will be found. 

Hollow

You will not need to dig out your own specimens, the hard work and basic preparation has already been done by the Dobells.  However, as you pick up, roll over and haul heavy specimens, likely under a merciless sun, you are going to discover something else.  Getting all those beautiful petrified wood pieces demands expertise and a lot of back-breaking labor.  It won’t take long to realize how much hard work Rhonda and her family have put into their business.  Bring plenty of water with you to drink and to pour on the rocks to get a better sense of the colors that would be brought out by polishing.

Specimen tumbling

Specimen for tumbling

The Dobell Ranch abuts the Petrified Forest National Park and a short drive will take you to the park entrance.  Next to the Visitor Center you can see quite a number of impressive specimens exposed on the surface and get an overview of the harsh badlands that compose the region.

PFNP overlook

Petrified Forest National Park

We inhabit an amazing world.  No humans ever saw these trees of the Triassic when they were alive, but we have a very good idea what some of them looked like so long ago.

 

An image gallery of Dobell Dig Site specimens courtesy of Larry Jensen

 

PetWoodDoBell18-04

 

PetWoodDoBell18-02

PetWoodDoBell18-03

PetWoodDoBellAZ18-08

 

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