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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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Eradicating Malaria With Gene Drives – Steering Past Hype-etheticals

Malaria is a longstanding threat to human health and wellbeing.  Could CRISPR-based gene drive technology be the single best hope to end to this scourge (1)?  Are we poised to eradicate malaria by simply deciding to release gene drives?     

Disentangling Hypothesis and Hype

Malaria is caused by parasitic microbes transmitted by mosquito bites and mosquito abatement is the tried and true way to break the chain of disease transmission.  Gene drives designed to attack malaria transmission at its mosquito vector source are said to be ready to go (1) although this depends on how one defines the term ‘ready.’

Aim

It is important to understand that using gene drives to antagonize malaria transmission is a promising, but unproven concept.  Significant questions have been raised about how well released gene drives might function in nature and possible risks associated with them (2, 3).  Statements that malaria could be eradicated and millions saved if only we decide to use this miracle technology at this stage are hope and hype.                

Lives Are at Stake, What to Do?

When it comes to controlling mosquito-borne diseases, there have traditionally been few limits on vector eradication efforts.  Humankind has never hesitated to physically alter the environment to suppress mosquito reproduction and when such measures did not suffice, use indiscriminate, murderous insecticides.  Perhaps precisely targeted extinction drives – if they work – will offer a less destructive alternative approach.  Mindful that human lives are in the balance (1) it becomes important to cut through the promotional hype to reach a sober judgement as to when gene drives will actually be ready for use and what other strategies should be pursued in the interim.        

Malaria is an elusive adversary, but although scientifically alluring, gene drives are far from being the sole hope to control this disease.  Development and testing of a vaccine to prevent Plasmodium falciparum malaria has advanced significantly (4).  Instead of counting on gene drives to be the final solution, more lives might be spared more quickly by following a more traditional vaccines development avenue as a top priority.  The program to control poliomyelitis epidemics in the mid-twentieth century provides an example.  Frustrated with slow progress toward a cure, the foundation funding infantile paralysis research opted to support a less scientifically elegant killed virus strategy of Jonas Salk.  Although not deemed ground-breaking by peers, that decision to enable Dr. Salk to build on the results of others and emulate the success obtained against influenza viruses turned out to be the fast track to eliminate polio paralysis epidemics (5).  Both killed virus and the years later-arriving live attenuated vaccines remain critical elements in on-going efforts that have now driven polio paralysis to near total extinction.         

Acknowledging the Malaria Story is Complicated

In some parts of the world the threat of malaria has been curbed tremendously using public health measures and vector control strategies.  However, malaria remains a stubborn danger in other regions, perhaps reminding us that seeking a universal solution to such geographically far-flung and adaptable disease agents may be unrealistic.  A diverse set of approaches – combining public health measures, vaccines, and possibly gene drives – may be necessary to achieve the ultimate goal of the world-wide elimination of malaria.  With CRISPR technologies we may be entering an age of miracles and additional research could prove gene drives are the ultimate answer to malaria.  However, even a miracle still may not provide the shortest road to controlling this scourge.     

PigFly  

(1) Dylan Matthews.   A Genetically-Modified Organism Could End Malaria and Save Millions of Lives – If We Decide to Use it.  Vox.com, 31 May 2018. mitsha.re/CK8M30kibbB

(2) Carl Zimmer. Gene Drives Are Too Risky for Field Trials, Scientists Say.    The New York Times, 16 November 2017.    https://www.nytimes.com/2017/11/16/science/gene-drives-crispr.html

(3) Ewen Callaway.   Gene Drives Thwarted by Emergence of Resistant Organisms.  Nature, 31 January 2017. https://www.nature.com/news/gene-drives-thwarted-by-emergence-of-resistant-organisms-1.21397

(4) Jen Christensen.   First Malaria Vaccine to be Widely Tested in Africa Next Year.  CNN, 26 April 2017.  https://www.cnn.com/2017/04/24/health/malaria-vaccine-trial-who/index.html

(5) Gerard Piel.   How the March of Dimes Got Behind Dr. Salk – Letter to the Editor, The New York Times, 26 June 1995. https://www.nytimes.com/1995/07/01/opinion/l-how-the-march-of-dimes-got-behind-dr-salk-137095.html

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The Drive to Vanquish Malaria – Which Road to Follow?

The news article (1) begins with some bold declarations – CRISPR gene drive technology is the single best hope to end malaria and spare the lives of millions.  Malaria is a deadly menace and eradicating it would save multitudes from debilitation and death.  I agree with the author completely regarding the gravity of the situation and the idea the potential for gene drive technology to control or eliminate human disease due to malaria must be investigated.  The other brash statements?  Not going down those roads.     

Where Are We?

A gene drive expert, Ethan Bier, maintains that pending regulatory approval, the technology to attack malaria transmission at its source is virtually ready to go (1).  It was not clear whether Dr. Bier’s projected time line was for an extinction drive, an “alleviation” drive to render mosquito hosts unable to host the malaria parasites or both. 

The article provides some context for readers regarding the history of gene drives and an insightful breakdown of the various strategies employed by researchers to vanquish malaria.  Is it true “the hardest part of the development phase is over”?  Perhaps, but we will have to see how effectively gene drives actually work in natural ecosystems.  Although there are several approaches, this is untested technology and questions have been raised (2).

Controversy Ahead 

The political battles as to how gene drives will be tested and perhaps broadly deployed have just begun.  Aware of potential public sensitivities at least one group may execute a step-by-step, trust-building strategy initially centered on the release not of gene drives, but mosquitoes engineered to be sterile (1).  Only after malaria suppression using ephemeral populations of genetically modified mosquitoes is demonstrated successfully will gene drive releases be considered.  The sterile insect technique to control disease has been extremely successful (3) and genetically modified mosquitoes created to suppress human diseases have already been tested in some locations.  However, public acceptance of gene drives is by no means assured and perhaps a series of carefully calibrated steps will turn out to be a wise choice.  The political choices ahead are likely to hinge as much on public relations as scientific data.

Confused

Gene Drive Backlash?

Some groups are not enamored with the basic concept of permanent ecosystem genetic modification through gene drives.  But could writing a “bad” article that merely impedes gene drive use end up killing children – thousands of them? (1).  Overblown proclamations may make gene drive proponents their own worst enemies.  Other actions might inadvertently provide superb talking points for potential adversaries as well.

When it comes to malaria control, gene drives are not our only hope as the article (1) makes clear.  Further, although we may be poised to field test gene drives, at this point such actions are in no way equivalent to taking concrete steps that will eradicate malaria.  Notwithstanding the article title (1) this is research and the ultimate outcome is in doubt.  How many can’t miss, sure fire concepts have fizzled when put to a real test?  Presenting gene drives as the answer to the scourge of malaria is premature and scientists should be both cognizant and sensitive to the dangers of getting too far ahead of the actual test results.  In addition, it is important to recognize the habitual tendency to justify gene drive use by layering unproven hypotheses on top of one another.  We do not know how well gene drives will perform – it is misleading to claim they are safe because a gene drive “can be reliably countered by overwriting the unwanted changes” with another gene drive (1).  This is not a data- or experience-based rationale, it is soothing supposition.  These opinions masquerading as justifications have been repeated to the public for quite a while and it is time for the experts and scientific community to speak with more precision.

Are we getting the whole story of malaria control efforts?  It depends on the articles you read and news sources you follow.  The situation is urgent, but some progress has been made in other areas (4).  Most important, significant strides have been made in the development of a vaccine to protect against Plasmodium falciparum malaria with initiation of a wide-scale pilot project phase imminent (4, 5).  Acceptance of a vaccine is not automatically guaranteed, but this competing technology seems to be coming to fruition.  To the guy with a gene drive the road to a cure might appear straight and narrow, but perhaps the quickest route to vanquishing malaria or Lyme disease [Lyme Disease Research – A Stalking Horse for Gene Drives? ] will be to focus on a proven technology. 

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(1) Dylan Matthews.   A Genetically-Modified Organism Could End Malaria and Save Millions of Lives – If We Decide to Use it.  Vox.com, 31 May 2018. mitsha.re/CK8M30kibbB

(2) Ewen Callaway.   Gene Drives Thwarted by Emergence of Resistant Organisms.  Nature, 31 January 2017. https://www.nature.com/news/gene-drives-thwarted-by-emergence-of-resistant-organisms-1.21397

(3) IAEA.  http://www-naweb.iaea.org/nafa/ipc/screwworm-flies.html

(4) Jen Christensen.   First Malaria Vaccine to be Widely Tested in Africa Next Year.  CNN, 26 April 2017.  https://www.cnn.com/2017/04/24/health/malaria-vaccine-trial-who/index.html

(5) Fahmida Miller.   Ghana, Kenya and Malawi to Pilot World’s First Malaria Vaccine.  Al Jazeera, 25 April 2018.  https://www.aljazeera.com/news/2018/04/kenya-roll-worlds-malaria-vaccine-180425080815044.html

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Gene Drives – Will Conqueror Biomolecular Bots Dictate a New Book of Life?

Declining vulture populations have received some recent news coverage. The number of human rabies cases in India is not known which makes it difficult to establish clear correlations between vulture population losses and human rabies increases. However, the notion some ecological changes yield unanticipated consequences and potential health risks still holds.

JayVay

Gene Drives – Will Conqueror Biomolecular Bots Dictate a New Book of Life?
By Guest Blogger,
Tyler Kokjohn, Ph.D.

 A new DNA engineering technique known by the strange name CRISPR-Cas9 allows scientists to edit the genomes of living cells with unprecedented ease and precision (1).  The method has only been in wide use for a few years, so it is hard to envision all the breakthroughs it will foster.  However, it is already clear the implications will extend far beyond the laboratory and clinic.

Conqueror WormThe CRISPR-Cas9 DNA editing system is versatile, but scientists have extended its capabilities by creating powerful new forms of this technology which function as gene drives (2).  A gene drive disperses genetic alterations or DNA cargo rapidly through a population by overruling the normal patterns of inheritance.  A recipient of a gene drive receives the complete genetic information needed to synthesize the enzymes and guide…

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Never Sell the Clones

Sunday evening, March 11, 2018, 60 Minutes aired a story about how cloned ponies have infiltrated polo in Argentina (1).  A multi-faceted account reported by Lesley Stahl, it is well worth your time.

An accident involving a prized pony may have started it all.  Before the animal was euthanized, the owner, a champion polo player and noted pony breeder directed a veterinarian to preserve skin cell samples.  In 2006 he was anticipating the day might come when it would be possible to resurrect his lost pony.  His foresight paid off.

Several animal species have been cloned and the technology is generally available.  However, the work is complicated and expensive making the cloning of companion or champion animals a game for the well-funded (2).  Using cells harvested from several of their best horses the polo breeders have created more than 100 clones.  These activities are legal and permissible under the rules of polo.   

ponies

Nature vs. Nurture Again

Does having the right genes make a champion polo pony or are a good environment and proper training the most important factors?  The 60 Minutes program reveals the clones are raised in a truly extraordinary environment featuring special diets, expert care and superb training.  Despite some subtle physical differences, the discussion that the clones possess the aptitudes and dispositions of their progenitors is quite interesting.  No claims are made that the clones are totally identical to their ancestors – some spontaneous mutations, mostly inconsequential, will always be present.  In addition, the clones are produced in surrogate mares.  That means the gestational environment will be close, but not identical to, the conditions for the originals.  Environmental conditions exert some influence over gene expression and development.   

Couldn’t expert breeders accomplish the same thing as the high-tech cloners?  In one sense they already did exactly that – the clones were derived from ponies created by just such methods.  The other consideration is that the clones beg the question as to which animals are the best – that decision was already made and carried forward into the future through cloning.  But, can anyone be sure that donor animals selected possessed the best polo pony genetic profile there ever can be?

The ultimate test for polo ponies is success on the field of competition.  In a championship match of clones vs. breeders, the clones prevailed by the narrowest of margins (1).  Perhaps this reflects the fact that the human riders also play a significant role in the competition.  In a situation where both horses and riders are top flight, it would appear cloned ponies did not offer any huge competitive advantage.

As is the case for ponies produced in the traditional ways, the value of clone-sired foals is based on the pedigree of their ancestors.  Cloned ponies are mated with champion stock and the foals may command a high price – sold for a reported maximum price of $250,000 (1).  The pony breeder/cloner interviewed noted something interesting about the fate of the cloned animals.  They are never sold.  The reason is simple, if you marketed them it would not be long before everybody had the same miracle stock.  End of mystique and/or competitive advantage.   

The Future                             

The amount of tissue needed to clone a champion polo pony is small and perhaps misappropriation of clones will become a problem.  Or the issues of safeguarding clones might get even more complex.  It may become necessary to update the definition of clone (3) yet again as scientists begin developing more powerful genetic manipulation technologies (4).  For example, what if new technologies allow someone to take the genomic sequence of a champion and simply introduce all the genetic changes that turn an ordinary animal into a proven top performer?  Is that clone infringement?  As the cloners should understand, each new technology opens up new possibilities.  The cat-and-mouse intrigues of elite Olympic athletes attempting to gain advantage (5) suggests that competitive forces might spur the emergence of a genomics high technology race in the polo pony world of the future.

Never Sell the Clones

For now, polo pony foals derived from champion stock are valuable.  However, it is uncertain how much genetic variability exists in breeding stocks.  Perhaps there is a magic genetic profile that only the champion animals possess.  It may not take long to determine if that is true.  Refusing to sell clones is a brilliant, if potentially temporary, business strategy.  In the future persons unable to purchase a genetic champion pony may be able to construct one of their own.       

 

Thanks to Carol Rainey for making certain I saw the 60 Minutes story on polo pony clones.   http://www.carolrainey.com/

 

(1) Lesley Stahl.   The Clones of Polo.  60 Minutes, (CBS News), 11 March 2018.  https://www.cbsnews.com/news/the-clones-of-polo/

 (2) Matt Stevens.   Barbra Streisand Cloned Her Dog. For $50,000, You Can Clone Yours.  The New York Times, 28 February 2018.  https://nyti.ms/2COao5l

(3) National Human Genome Research Institute.   https://www.genome.gov/25020028/cloning-fact-sheet/

(4) D. Boeke et al. 2016.  The Genome Project-Write.  Science, 8 July 2016, [353(6295):126-127]. http://science.sciencemag.org/content/353/6295/126.full

(5) Bret Stetka.   Have We Reached the Athletic Limits of the Human Body?  Scientific American, 5 August 2016.  https://www.scientificamerican.com/article/have-we-reached-the-athletic-limits-of-the-human-body/

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