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Synthetic Genetic Shakespeares

Examining the implications of science and technology

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Will Scientific Research Validate the “Twinkie Defense”?

The murders of San Francisco mayor George Moscone and city supervisor Harvey Milk by Dan White created a media sensation 40 years ago.  Part of the public uproar involved a diminished capacity alibi employed by Mr. White’s lawyers that was repackaged by others as the captivating “Twinkie defense” (1).  The central tenet of the alleged Twinkie defense was that consumption of sugary junk foods impaired the defendant’s mental capacity.  Although the actual legal defense revolved around the consequences of Mr. White’s untreated depression, part of the evidence brought forth was his switch to an unhealthy diet.  The mis-characterized trial strategy provoked public outrage and was established as an urban legend (1). 

Not long after this shocking trial had concluded I was a graduate student being introduced to the biochemistry of neuronal cells by Professor Michael Collins.  I recall Dr. Collins discussing the Twinkie defense, indicating that although the public perceptions about it may not have been completely accurate, neurons were sensitive to their environments.  Although not much direct evidence was in hand at that time, Dr. Collins did not dismiss the possibility dietary choices might substantially impact human behavior.  Science may soon have a great deal more to say about such matters.

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Researchers are now tracing out the complex biochemical transactions that take place between human beings and the invisible microbes living in and on us (2).  It turns out that the benefits of a healthy, high fiber diet actually reach us indirectly through the metabolic transformations produced by a diverse community of active microorganisms.  Gut microbes, our personal gastrointestinal microbiomes, are influenced by diet and, in turn, feed back essential, health-maintaining signals to our cells.  Evidence is accumulating that gut bacteria may synthesize or regulate the levels of key neurotransmitters such as serotonin that are known to play important roles in disorders such as depression (3).

The discoveries revealing the intricate interactions between gut bacteria and the brain hint we may see new ways to mitigate some significant human health issues.  If such notions are validated, could the findings herald the transformation of the Twinkie defense from inaccurate legend into a compelling, scientifically-grounded legal strategy? 

Then again, perhaps the lawyers of the future will never need it.  If we comprehend how dietary choices influence behavior, scientist-nutritionists of the future might devise new foods (4) and probiotic programs to keep us all happy and well-behaved in a brave new world.  

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(1) David Mikkelson.   The Twinkie Defense.  Snopes.com, 27 August 2009.  https://www.snopes.com/legal/twinkie.asp

(2) Carl Zimmer.   Fiber is Good for You.  Now Scientists May Know Why.  The New York Times, 1 January 2018.  https://t.co/tCfReMWXaj

(3) David Kohn.   When Gut Bacteria Change Brain Function.  The Atlantic, 24 June 2015.   https://t.co/XpU4K5PMug

(4) Barbara J. King.   Clean Meat, Via Lab, Is On the Way.  NPR, 2 January 2018.  https://t.co/UJ71m9B9Eo

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Preserving Odd Connections

Years ago, during the Christmas season, I would often find my way to a used book store in Cedar Falls, Iowa.  It was a delightful jumble – all sorts of pearls scattered here and there, each embedded with a not-so-faint cigarette odor that came home with them.  It took a long time to go through the place, but I was usually rewarded with finding something I had no idea I wanted until I actually laid eyes on it.  Until recently I did not comprehend the full value of the service this little store had provided me.            

A story in The New York Times today noted the passing of Book World, the 4th largest U.S. bookstore chain with over 40 stores (1).  These are hard times for retail in general and book sellers in particular.  The depressing truth be told, these losses confirm it is tough to compete with the internet merchandizers these days.

This story reminded me of an article I first noticed on Twitter a few days earlier about the joys and difficulties of finding books that fall outside personal experience (2).  True enough, the software enabling us to browse Amazon or other internet sites is helpful, but these wonderful tools may also be inadvertently constricting.  It can be tough to discover something really novel when you have no idea of what items to search or rely on suggestions based on items purchased by others who bought the same book.  Maybe the current software workaround for persons determined to expand their horizons is to enter in some random words and just see what pops up.        

Although some programs are better than others (2), suffocation by search algorithm is one facet of emerging changes that collectively diminish the chances we will stumble on unanticipated gems while shopping.  Making the effort to get to local retail outlets is not always the final solution because stores must organize their stocks in some manner and, as noted by Ms. Schwab, “… the more we categorize, the less we are likely to discover.”  However, pacing a real bookstore does at least give more opportunity for fully serendipitous discoveries.  Mulling over this situation it finally dawned on me how that dusty, smoke-laden and rather wonderfully disorganized used book store was actually a well disguised treasure filled with unique opportunities for discovery.

Will finding mind-bending reading become tougher in the future as bookstores vanish?  Maybe Amazon will find a way to devote a corner of their new bricks-and-mortar stores to used books.  If we are really lucky they will allow them to be kept in an untidy fashion unsupervised with powerful computer algorithms or curated by neatness-obsessed managers.  Nature preserves for untrammeled explorers trapped in a homogenized world, the magic of odd connections might still occur in such places.

 

Books

 

(1) David Streitfeld.   Bookstore Chains, Long in Decline, Are Undergoing a Final Shakeout.  The New York Times, 28 December 2017.  nyti.ms/2lePwhN

(2) Victoria Schwab.    Just Trust Me:  In Praise of Strange Books.  NPR, 23 December 2017.  twitter.com/npr/status/945…

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Forever Young Through Plasma Infusions?

If you want to recapture your lost youth there may be something far more potent than Botox – rejuvenating infusions of plasma harvested from young persons.  The idea has gained sufficient scientific currency to spawn new start-up companies to investigate and/or capitalize on it (1, 2).

Experiments with mice have demonstrated that blood from young animals reversed the negative changes on brain structure and cognitive function characteristic of advancing age (3).  A recently completed small-scale follow-up study suggests persons with dementia who received plasma taken from donors between 18-30 years of age experienced an improvement in their ability to cope with the activities of daily living.  No one is suggesting plasma therapy will cure Alzheimer’s disease (AD), but dementia has been an intractable medical problem for so long any good news draws attention.

Details are Sketchy and Sometimes Mice Lie

The full details of the dementia study will be presented soon.  Notwithstanding hope, it is important to keep in mind that this work, while controlled, was a small-scale trial of the type used to establish a treatment is safe and well tolerated.  At this point no claims have been made that the treatments significantly improved cognitive function, there are only hints providing plasma from young donors might have helped demented subjects get along better with day-to-day living.  In addition to being small, the study was short duration – 4 weeks – so at this time whether the beneficial impact observed is deemed real or lasting is entirely speculative.  Additional details such as the level of dementia of the experimental and control groups, how they were assessed and the magnitude of differences between them will be apparent when the data are presented to the public.  As matters stand the results may support performing a larger scale study.  However, it is too soon to tell if periodic infusions plasma acquired from young donors are the secret route to eternal youth or a way to stave off AD dementia.  Caveat emptor to potential investors; when it comes to AD cures everything works in mice and the people doing the study are involved with a company seeking to develop plasma infusion therapy. 

A New Set of Problems – What if Young Blood Revitalization Actually Works?

Recapturing youth through plasma infusions is a wealthy person’s fantasy.  Despite almost zero evidence for efficacy, people have paid a reported $8,000 (USD) per dose to receive pooled plasma infusions (1).  If experiments confirm young-donor plasma does nothing more than stop dementia progression the results will be sensational.  Because millions currently suffer from AD, demand for young-donor plasma will immediately far exceed supply.  Biochemists will apply a standard divide-and-conquer strategy to identify the blood factor(s) responsible and that may pave the way to mass produce the essential ingredients to create dietary supplements or other ways to supply them.  However, until that is done young-donor plasma supplies will be too limited to meet the demand which suggests they will either be rationed or sold off to the highest bidders.  For quite a while only the wealthy will be able to buy their way out of AD.

Goop

Transhumanist Entrepreneurs to the Rescue?

Some intrepid souls are pushing DIY biohacking to the limits to bring a transhuman future into being (4).  Maybe such bold persons will help society transition into a free market mass rejuvenation era.  Those under 30 years of age could cash in as donors.  But what if we get more creative and allow parents to license the use of their children?    

Let’s do the math:

            Average cost to raise a child to age 17, adjusted for inflation (5)     $ 284,570

            Current retail price for pooled ‘young plasma’ treatment (1)                   8,000

Once you fatten your kids up to around 110 pounds or more (the legal size) and have them donating plasma every 60 days it should be possible to establish a positive cash flow to recoup the initial investment sunk costs or finance a college education.  In the event that regulations regarding donor age limitations are relaxed, having children could be positively lucrative.  Everybody will want one and I can already envision an app that connects youthful plasma donors to the elderly vampire demographic.  Should be a great gig until the biochemists figure out how to render children outmoded before they have entered the work force.

For those wondering how to remain forever young, there is no telling if young-donor plasma infusions are the answer.  Even if they do keep our brains working we cannot be sure they will iron out tell-tale wrinkles.  It might be a good idea to keep the Botox handy for a while. 

(1) Gavin Haynes.   Ambrosia: The Startup Harvesting the Blood of the Young.  The Guardian, 21 August 2017.  https://www.theguardian.com/society/shortcuts/2017/aug/21/ambrosia-the-startup-harvesting-the-blood-of-the-young

(2) Alison Abbott.   Infusions of Young Blood Tested in Patients with Dementia.  Nature, 1 November 2017.  http://www.nature.com/news/infusions-of-young-blood-tested-in-patients-with-dementia-1.22930

(3) Saul A. Villeda et al.   Young Blood Reverses Age-related Impairments in Cognitive Function and Synaptic Plasticity in Mice.  Nature Medicine 20:659-663.  https://www.nature.com/nm/journal/v20/n6/full/nm.3569.html

(4) Tim Adams.   When Man Meets Metal: Rise of the Transhumans.  The Guardian, 29 October 2017.  buff.ly/2lptnQs

(5) https://www.usda.gov/media/blog/2017/01/13/cost-raising-child

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Looking for Life on Mars – Are Scientists Running Out of Time?

Is it possible that scientists seeking evidence of life on the planet Mars are being too timid?  Have concerns over contaminating Martian environments with terrestrial microbes been exaggerated out of proportion to actual risks?  Will the imminent arrival of human explorers and colonists make all such precautions utterly futile?  A recent article makes a strong case that scientists hoping to capture pristine samples from Mars may have missed the opportunity (1).  And in the event the red planet has not already been seeded by terrestrial microbes transferred on

Earth and Mars

our scientific probes or the natural process of interplanetary panspermia, the author is concerned our efforts to avoid contaminating Mars will not matter much once humans arrive. 

Are Martian Ecosystems Vulnerable to Invasions or Not?

At this point it is impossible to say whether Martian ecology has been disturbed by microbes from Earth.  Our knowledge of terrestrial microbial ecology is rudimentary and Mars is a complete unknown.  On one hand it seems reasonable to assert that any Martian microbes would be so exquisitely adapted to their environments that no hitchhiking terrestrial bugs accidentally inoculated there could possibly displace them.  That would seem to make our laborious precautions to prevent transfer unnecessary.  However, introductions of exotic species have sometimes totally disturbed normal ecological balances and microbial invasions have been documented (2).  In addition, if Martian environments are sparsely populated or uninhabited they may be vulnerable to invasion (3).

Hypotheses vs. Facts

Although no spacecraft can be guaranteed to have been totally sterilized, systematic decontamination measures have been employed for Mars missions.  Terrestrial microbiologists accustomed to working in richly populated environments have developed mechanisms to acquire samples that are as free from extraneous contamination as possible.  Such measures make interpreting results much simpler.  Even though recent Mars missions have not been designed to search for living microbes, the minimal contamination strategy makes good sense scientifically.  Other than demonstrating, at great expense, intelligent life forms can successfully execute an artificial form of panspermia, recovery of invasive terrestrial vagabonds left behind by prior survey missions would not be a big advance.  But what if our spacecraft or natural panspermia have already inoculated Mars?  Is that possibility enough to jettison planetary protection protocols and greenlight missions into the Special Regions deemed most likely to harbor life or evidence of life?  Notwithstanding the fallout from abandoning formal treaty obligations to safeguard such places, the idea Mars has already been contaminated by human exploration or panspermia is an unproven hypothesis.  Scientists are unlikely to go along with such actions when the answer remains a matter of opinion.

Mars

The Humans Are Coming!

Does imminent human exploration or colonization of Mars force scientists to rush ahead and drop safeguards?  There seems little doubt that humans will transfer living microbes to the planet.  Even worse, spaceflight conditions might induce the evolution of microbes with unique and unpredictable properties (4).  Could all that be the end of any hope to analyze uncontaminated samples?  Again, the only thing more limited than our understanding of terrestrial microbial ecology is our knowledge of Martian ecology.  Only a miniscule portion of the Martian surface has been examined directly and even the Special Region designations are conjectural.  It is impossible to say if accidental contamination by previous missions carries any significant implications for the immediate vicinity, a region or the entire planet.  Until it can be proven that proactive protection measures and operational restrictions are futile, I doubt that mission planners will embrace the idea of removing them.  We have to see how the authorities – whomever they may be – will prioritize and accommodate future missions involving humans into the on-going plans to search for signs of life on the red planet.

Maybe We Have Already Driven Right Past Them

Could Mars and Earth have followed similar paths of physical and perhaps biological evolution for a time?  We see how microbial life on Earth has exploited even the most hostile environments so maybe Mars still has relict organisms holding on in scattered locations.  Or could conditions in spots be more hospitable than what we believe are representative for the planet as a whole?  Some terrestrial microbes thrive under environmental conditions that at first glance would appear to be completely inimical to them.  For example, cryptoendolithic microbes evade hostile conditions by taking shelter within rocks.  

CryptoDeemHills

 

Hot, dry desert ecosystems harbor algae which grow under light-colored stones where they find sufficient water and the right level of light to support photosynthesis. 

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RockAlgae2

 

Searching for life or signs of past life on Mars are complicated undertakings.  Perhaps the prospect of human arrivals will spur scientists to speed up their efforts.  We are about to go down some uncharted paths and explore totally unknown territories.  Maybe one of our rovers has already driven past rocks with native Martian microbes living in or under them. 

 

(1) Alberto G. Fairén.   Worries About Spreading Earth Microbes Shouldn’t Slow Search for Life on Mars.  The Conversation, 28 September 2017.  https://theconversation.com/worries-about-spreading-earth-microbes-shouldnt-slow-search-for-life-on-mars-84742

(2) Sarah A. Spaulding et al.   Diatoms as Non-native Species.   The Diatoms, 2nd edition, J. P. Smol and E. F. Stoermer, editors.  Cambridge University Press, 2010.    https://www.fort.usgs.gov/sites/default/files/products/publications/22437/22437.pdf

(3) Wilk-Wozniak and K. Najberek. 2013.  Towards Clarifying the Presence of Alien Algae in Inland Waters – Can We Predict Places of Their Occurrence?  Biologia 68(5):838-844.  http://www.iop.krakow.pl/pobierz-publikacje,536

(4) Nicola Davis.   ‘The Enemy Within’: Mars Crews Could Be at Risk From Onboard Microbes –Study.  The Guardian, 4 October 2017. https://www.theguardian.com/science/2017/oct/04/the-enemy-within-mars-crews-could-be-at-risk-from-onboard-microbes-study

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As You Like It – The Singularity Emerges

Facebook executives now admit they have created an entity they do not control completely (1).  As the company seeks ways to curb the malevolent aspects of their invention, observers have likened their predicament to the Frankenstein story (1).  We now seem to have arrived at the point in Mary Shelly’s novel where Dr. Frankenstein acknowledges his creature and strikes a bargain to satisfy his demands.  We will see how matters play out for Facebook.        

Personalized Mass Marketing

Whether the commandeering of Facebook functionality was predictable (2) or not it is important to understand how it seems to have been exploited.  Members are the center of attention of surveillance algorithms.  However, the real Facebook customers are advertisers and this mass marketing enterprise is a great service for them because it is so good at learning what each and every one of its 2 billion users likes (2). 

Click-bait as the New Truthiness     

As we view, linger over and actively ‘like’ content, Facebook artificial intelligence (AI) algorithms figure out what keeps us happy (2).  Because substantial numbers of members are willing to share information, the inter-member transmission process may become an infectious chain reaction.  With 2 billion users, commercial goals of supreme importance and little editorial oversight, results predictably have varied.  Facebook is the premier global news aggregator of the world wide web with a surprising tendency to promote information incest.  Indulging penchants does cultivate contented consumers.  But the software might also blinker users and the ease with which content can be shared could prompt us to forward materials that resonate regardless of their accuracy (3).  In fairness, Facebook was not created to educate the public.

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Facebook as the Harbinger

Scientists have speculated how biotechnology may be employed to create the perfect astronauts of the future (4).  Some of the proposals are sheer flights of fancy, but the fundamental philosophy of human beings reduced to instrumentality should look familiar.                    

Facebook has teamed artificial intelligence (AI) with internet-mediated infotainment to transform service-using persons into infinitely scalable and profitable data products.  By the time biotechnology allows a more physically concrete metamorphosis into living products we will be accustomed to the role.  The singularity is sneaking up on us.     

There are more shiny things to come.  Will we ‘Like’ them into reality?

(1) Kevin Roose.   Facebook’s Frankenstein Moment.  The New York Times, 21 September 2017.  https://nyti.ms/2ygvbg2

(2) Zeynep Tufekci.   Facebook’s Ad Scandal Isn’t a ‘Fail,’ It’s a Feature.  The New York Times, 23 September 2017.   https://nyti.ms/2jTyUhp

(3) Nina Jankowicz.   The Only Way to Defend Against Russia’s Information War.  The New York Times, 25 September 2017.   https://nyti.ms/2yneks9

(4) Antonio Regalado.   Engineering the Prefect Astronaut.  MIT Technology Review, 15 April 2017.  https://www.technologyreview.com/s/604142/engineering-the-perfect-astronaut/

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Scanners Live In Vain! vs. Frankenstein

The Implications of Purpose-Built Humans for Space Exploration

During the summers of my college years I was a laborer.  My job tasks included efforts like digging ditches, demolition projects and pouring concrete.  Often outdoor work, the weather conditions alone could be challenging. 

Too young to retire, too old to hire

A few of my coworkers were at least 40 years older than me.  With a lifetime of experience under their belts these guys had a wealth of great stories to share.  However, I did not understand the full significance of some of their accounts until many years later.  Before they were laborers Bill and Don held skilled journeyman positions at the local newspaper; parts of a team that made it possible to mass produce high quality documents 7 days a week, 365 days a year.  And then the owners invested in a new offset press printing process.  You know the rest of the story; the new methods were more efficient, less labor-intensive, etc., so Bill, Don and quite a few more people lost their jobs.  Worse, these guys had been cast aside at an awkward age – too young to retire and, in the opinion of many employers, too old to hire. 

Cruel Calculations

Bill showed me the art of using hammer and chisel to take apart concrete block walls.  His skills were exemplary and he explained that in his past life he fabricated chases (block frames for type) for old style newspaper printing presses by hammering lead into the proper form.  His hands showed the impacts of decades of diligent labor.  Don tried to describe the process he performed to transfer photographs to printing press plates, work that involved the use of a deep red-colored powder they called ‘dragon’s blood.’  He described how that red dust got on everything and that it really stuck on skin over the veins which apparently made for some hideous-looking workers.  I think (I hope) these people had dust masks, but maybe that was when management could still get away saying safety equipment was for the weak.

Those jobs required time to master and they took a toll, but the compensation was good enough to raise a family in reasonable comfort.  Over the many years their jobs changed Bill and Don physically and mentally, although we do not commonly think about these situations in such terms.  The mechanical skills and expert’s eye they developed were physically hardwired into their brain structure and the deft moves needed to execute the work became second nature.  Loyal, valued and valuable employees, they suddenly became worthless to the company and were shown the door.  Thank you for your service and good luck. 

When I met Bill and Don they had found work as custodians for the school district.  Part of their new jobs required them to work on whatever projects needed doing during the summer months.  So that year they were laborers breaking up concrete walls, hauling blocks and mixing cement.  The work could be exhausting for an 18 year-old and I can’t imagine how hard it must have been for them.  I never heard a complaint from either man, they were probably happy to have found a steady job with benefits.

Building Perfect Employees 

New technology, displaced workers, profits, loss and grief, the story heard over and over again.  No doubt similar stories will be repeated in the future although maybe they will be a good deal more complex.  A recent article (1) pondering how it might be possible to construct astronauts with enhanced capabilities to tolerate the extreme conditions of space travel has some interesting implications.  Could genetic modifications yield a literal new breed of space explorers impervious to DNA-damaging cosmic ray radiation?  Although engineering super-human astronauts is not imminent, some hypotheses are in early laboratory testing. 

Scanners2

The extremely radiation resistant bacterium, Deinococcus radiodurans, has a high capacity to repair DNA damage (2).  Perhaps tweaking genes to enhance DNA repair capacity would help cancer patients recover from radiation therapy (3, 4) or enable astronauts to work safely in environments with murderous radiation levels.  In pursuit of such goals one group is reported to be considering augmenting the levels of a protein regulator known as p53 which plays important roles in allowing DNA damage to be reversed and halting the start of cancer (1).          

The Transhumanist (H+) future is often envisioned as a machine-organism fusion, but the fact is that the age of human-directed evolution has not even begun.  If genetic modification becomes a practical means to build better humans its use will raise even more complex ethical questions than device fusions.  Genetic alteration of adult volunteers, in principle, could be managed using informed consent procedures.  However, if germ cells are modified all succeeding generations become involuntary participants which renders nonsensical any notions of meaningful informed consent.  For example, take the idea that small-sized persons might be superior astronauts (1).  Unless only small-sized persons are recruited or there are ways in the future to shrink adults, achieving this specific goal would seem to require genetic changes be made early in life.  Could a child make such a decision?  If germ cells were altered would the involuntarily downsized descendants of the future wish they could be of average stature?  If they do could the genetic changes be reversed?

geneticvariationNIH

The Disposable Employee

Clearly, the first intrepid souls who are transformed into super-human space explorers will be taking a risk.  What happens when the job is done or the employer is done with them?  Our society tolerates risk exposure and even life-threatening occupational danger.  Today persons may elect to participate in biomedical research that could produce severe adverse outcomes.  And even though enlistment might lead to death or severe injury, military ranks are filled with volunteers.  Bill and Don were 20th century examples of the personal costs exacted by disruptive technological change.  In the 21st century it will be possible for clever lawyers to argue that clear precedents exist allowing corporations to subject genetically or otherwise engineered employees to risk and jettison them as deemed necessary.  In essence we are talking about the same thing – job-related changes in employees – imposed through different means in different centuries.  While Bill and Don restructured their brains and bodies on their own through long practice, some changes in the workers of the future may be accomplished with genetic manipulations.  Indeed, the argument could be made that by making a job less potentially damaging genetic modifications are more humane than the old style of employee management.   From the artisan weaver Luddites, 20th century journeymen like Bill and Don to the working persons of today and beyond, it seems the tradition of the disposable employee will continue as it has for hundreds of years.

What are the Implications?

Few things change faster than high technology.  Maybe the brave augmented once-human astronauts to come will have the foresight to negotiate terms that will protect them from hardship should new technologies render them obsolete.  Imagine an engineered astronaut with super human DNA repair capacity.  If his or her job is declared ended, maybe it will turn out the genetic alterations are irreversible because a fantastically efficient repair system will not allow any new changes to be introduced in DNA.  It is not clear if super DNA repair capacity has other costs; those impacts come out later.  Perhaps employers seeking volunteers will find it necessary to offer contracts guaranteeing full health care coverage and financial safeguards for genetically engineered employees.  Maybe the next battle will be cost-conscious corporations arguing that former humans have fewer legal rights than authentic humans.   

What if something unexpectedly good happens in genetically altered persons?  Even discoveries that seem positive at first glance might end up being problematic.  We are entering uncharted medical territories and maybe we will find that enhanced DNA repair and other tweaks to create super astronauts have rejuvenating, anti-aging effects.  Once it is recognized that super astronauts out-live normal humans by wide margins, large segments of the public will want that alteration.  Imagine organizations on the hook for pension cost payouts that last for centuries.  Think about social security.  Imagine the house you could own if you financed it through a 500-year mortgage.  Trying to get these strategies to work, scientists will be focused on the technical details at microscopic and molecular scales.  It will fall to others to recognize the necessity to carefully ponder the big picture and envision the full scope of what scientific success might ultimately bring.

The morality and ethics of human genetic modification will soon be vexing societies.  Cordwainer Smith examined the implications of the abandonment of home, well being and humanity in his science fiction short story Scanners Live In Vain!  We will do well to remember that while we have a long tradition of declaring human beings obsolete, nothing goes out of date faster than our instrumentality.  Will we explore space as true human beings or servile entities devised by and derived from humans? 

After reading Cordwainer Smith, you may wish to review Frankenstein; or, The Modern Prometheus by Mary Shelley.  Confusing the fact that Frankenstein refers to Victor Frankenstein, the scientist/creator, and not his un-named creation is a common error.  In the future this mistake may be more understandable if we make the momentous decision to play both roles.         

(1) Antonio Regalado.   Engineering the Perfect Astronaut.  MIT Technology Review, 15 April 2017.  https://www.technologyreview.com/s/604142/engineering-the-perfect-astronaut/

(2) S. E. DeWeerdt. 2002.  The World’s Toughest Bacterium. Genome News Network, 5 July 2002.    http://www.genomenewsnetwork.org/articles/07_02/deinococcus.shtml

(3) J. Li et al. 2017.  A Conserved NAD+ Binding Pocket That Regulates Protein-Protein Interactions During Ageing.  Science 355:1312-1317.    http://science.sciencemag.org/content/355/6331/1312.full

(4) Alice Park. Scientists Can Reverse DNA Aging in Mice.  Time.com, 23 March 2017.  http://time.com/4711023/how-to-keep-your-dna-from-aging/

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It’s Alive! The Most Terrifying Message of Frankenstein

 

Mary Shelley’s masterwork, Frankenstein; or, the Modern Prometheus will reach the 200th anniversary of its publication in 2018.  Spawned by a nightmare (1) her deeply horrifying work remains relevant in the 21st century.

Frankenstein overflows with messages, but has become a universally recognized, often weaponized, symbol of scientific overreach.  Everyone knows at the most visceral level that you do not want to go there.  Two centuries later science keeps going there.

The specific scientific issues of concern have changed, but the basic, fear-provoking story line of desecration, dominion and unintended consequences remains readily recognizable.  Twenty years ago it was test-tube babies (1) and the tragic death of Jesse Gelsinger (2), today we debate the wisdom of writing synthetic genomes (3) and fret over editing the germ line (4).

Perhaps we do not resolve the issues raised by scientific progress so much as adapt to them.  Dr. George Church and Ed Regis contend (5) that as new technologies are perfected and adopted by more persons, resistance to their use fades.  However, even though many persons have been willing to bet on stem cell therapies, the U. S. environment for stem cell research has been turbulent.  Perhaps would-be gene editors and genome synthesizers will emulate past efforts (1) and dictate decisions to use new technologies based on demonstrated mastery of technical details of safety.  Maybe this time the public or their elected officials will prove more distrustful of elite scientists and force a moral reckoning that has long been avoided.                                   

Mary Shelley ended Frankenstein with the creature vowing to destroy itself on a funeral pyre and disappearing into the icy Arctic darkness. 

I shall ascend my funeral pile triumphantly and exult in the agony of the torturing flames

Wretchs plan

With Frankenstein the creator dead and the creature vanished, the story would seem to have reached a satisfying climax.  But the final plan could not be executed for there would be no tinder in the Arctic wasteland to build the cleansing fire.  The wretch who knows better than anyone the consequences of poorly contemplated actions has come full circle by embarking on a mission without envisioning all the implications.  The most horrifying and timeless message of Frankenstein is its inconclusive ending.  To be continued…

(1) R. Haynes. 1998.  Myths that Won’t Die.  Review of Frankenstein’s Footsteps: Science, Genetics and Popular Culture by Jon Turney.  Nature, 20 August 1998 (394:735-736).    http://www.nature.com/nature/journal/v394/n6695/full/394735b0.html

(2) S. G. Stolberg. 1999. The Biotech Death of Jesse Gelsinger. The New York Times, 28 November 1999.   http://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html

 (3) J. 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

(4) D. Baltimore et al. 2015.  A Prudent Path Forward for Genomic Engineering and Germline Genetic Modification.  Science, 19 March 2015 [348(6230):36-38]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394183/

(5) G. Church and E. Regis. 2012.  Regenesis. How Synthetic Biology Will Reinvent Nature and Ourselves.  Basic Books, New York.

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Science Gets Serious About Dementia Prevention

The Grim, But Not Hopeless, Situation

An expert commission has concluded the number of persons afflicted with dementia is rising across the world.  However, the evidence also suggests it is possible that up a third of dementia is avoidable (1).  Along with medical interventions to control obesity, diabetes and hypertension, getting an education, maintaining social engagement and exercising may decrease dementia development risk.

The Alzheimer’s Disease Plot Thickens

Dementia is a general outcome associated with several distinct neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Lewy body disease among others.  Although temporary mitigation of symptoms is possible for AD and PD patients, no cures are in hand.  Scientists hypothesize that accumulation of amyloid-beta (Aβ) molecules is a critical factor in the emergence and progression of AD dementia.  Post mortem examinations of persons presumed on the basis of clinical findings to have Alzheimer dementia revealed about a third of them harbored surprisingly low levels of Aβ (2).  In addition, studies of healthy ‘oldest-old’ subjects have demonstrated that many harbor AD neuropathology while retaining completely normal cognitive function (3).     The implications are profound – these observations suggest the idea AD dementia is a direct consequence of Aβ deposition in the brain may be too simple.  Patients we have lumped together on the basis of clinical findings as AD dementia are biochemically diverse.  Curing AD dementia will not always be a matter of getting rid of Aβ deposits because some patients don’t seem to have them or are not affected by them.  Worse, many clinical trials were performed with subjects presumptively diagnosed as suffering from Alzheimer’s dementia on the basis of clinical findings.  These groups were probably heterogeneous in terms of their amyloid pathology (2), complicating how the success or failure of the experimental treatments were judged.  That means even if we had a cure for amyloid-induced Alzheimer’s dementia we might have missed it because they would have had no impact in trial participants who lacked Aβ deposits.

Eaten brain

A Holistic Approach to Dementia            

Scientists have initiated several clinical trials of AD treatments on persons with mutations known to produce early-onset AD dementia (4).  Because these subjects are certain to develop AD, it is possible to initiate therapy before dementia is evident.  If these interventions prevent or delay AD onset it will spark a rush to begin wide-scale use.  However, the treatments being tested today are expensive to produce and difficult to administer, so it is unclear how and when the tremendous demand for them will be met.

The situation is that for a long time many of us will remain at risk for dementia development.  Scientists have some ideas as to actions that might help prevent or slow the appearance of dementia, but multiple, systematic studies are now being planned (5).  Hopefully, the new information will lead to reliable conclusions as to how to avoid dementia.  Those efforts may be the best hope for most of us for some time.

Past history shows it is possible to control a mysterious and completely incurable disease. Unraveling the story of Kuru, the fatal transmissible spongiform encephalopathy of the Fore people of Papua, New Guinea, required the combined efforts of physicians, neuroscientists, geneticists and anthropologists (6).  Despite a complete absence of effective medical treatments, systematic study provided the knowledge and capacity to essentially drive Kuru to extinction.

A growing mass of evidence suggests a substantial fraction of dementia is preventable.  Scientists are now launching systematic explorations into how we might be able stave off this troublesome foe.

(1) T. Fagan. 2017.  Lancet Commission Claims a Third of Dementia Cases Are Preventable.  Alzforum, 11 August 2017.  http://www.alzforum.org/news/conference-coverage/lancet-commission-claims-third-dementia-cases-are-preventable

(2) S. E. Monsell et al. 2015.  APOE4 Carriers and Non-Carriers with the Clinical Diagnosis of Alzheimer’s Dementia and Minimal Amyloid Plaques. JAMA Neurology 72(10):1124-1131.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833059/

(3) C. L. Maarouf et al.  2011.  Alzheimer’s Disease and Non-demented High Pathology Control Nonagenarians: Comparing and Contrasting the Biochemistry of Cognitively Successful Aging.  PLoS One 6(11):e27291.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210154/

(4) P. Belluck.  2010.  A Thief of Memory Stalks a Colombian Family.  The New York Times, 2 June 2010.  https://nyti.ms/2vy8zZL 

(5) M. Chicurel.  2017.  New Dementia Trials to Test Lifestyle Interventions.  Alzforum, 11 August 2017.  http://www.alzforum.org/news/conference-coverage/new-dementia-trials-test-lifestyle-interventions

(6) P. P. Liberski.  2013.  Kuru: A Journey Back in Time from Papua New Guinea to the Neanderthals’ Extinction.  Pathogens 2:472-505. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235695/

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How Are You Feeling? Let’s Have a Look Online

If a new study is correct, physicians trying to gauge whether or not you are depressed may soon be interested in having a close look at your Instagram posts (1).  Because they reveal a great deal about behavior, Instagram posts and possibly other social media activities may turn out to be invaluable databases for mental health care practitioners.

The ability to sift through large aggregates of digital information has given epidemiologists new power to discover influenza epidemics as they emerge (2).  Predictive analytics based on marketing data can already offer retailers amazing – and profitable – insights into the needs of their customers (3).  Recognizing the potential, health care professionals have adopted social media to facilitate communication with patients (4), although the potential diagnostic power of these tools remains largely untapped.

Could we reach a point where computer analyses of Instagram posts become an important addition to the standard methods for diagnosing depression?  Nothing is certain yet, but perhaps this tantalizing prospect will remind predictive analytics scientists that the time is ripe for burgeoning digital information troves to make important contributions to medicine.  For example, the pathological changes of Alzheimer’s disease (AD) are thought to develop silently years before clinical signs and symptoms of dementia become obvious.  However, a retrospective analysis of the published works of author Iris Murdoch reveal the probable imprint of AD before she received a formal, and ultimately pathology-confirmed, diagnosis (5, 6).  This is where Google data scientists might now make a seminal contribution by analyzing written communications such as e-mails and assessing how they may have changed over time to identify the early linguistic signals that flag future AD. 

predictive-analytics

Analyses of Gmail might achieve something well beyond the current capabilities of medical science – recognizing young subjects at high risk for AD decades before even subtle signs of dementia begin.  A detailed study of women in religious orders revealed that the writing style and content of autobiographical essays written when they first entered their vocation predicted the individuals most likely to be afflicted with AD at the end of their lives (7, 8, 9).  Advance knowledge may enable at-risk persons to alter diet and other behaviors to mitigate the threat.  If the conclusions of the Religious Order study are correct it gives us hope that although writings might reveal AD risk, the final outcome is not necessarily etched in stone.

What you say and how you say it online have important health implications. It is time to harness the healing power of social media and digital communications.   

 

(1) N. Chokshi. 2017.  Your Instagram Posts May Hold Clues to Your Mental Health.  The New York Times, 10 August 2017.  https://nyti.ms/2uJePdQ

(2) G. Eysenbach. 2006.  Infodemiology: Tracking Flu-related Searches on the Web for Syndromic Surveillance.  Proceedings of the American Medical Informatics Association (AMIA) Symposium 2006; 244-248 http://www.webcitation.org/5LIlQNbDQ

(3) C. Duhigg. 2012.  How Companies Learn Your Secrets.  The New York Times Magazine, 16 February 2012.   http://www.nytimes.com/2012/02/19/magazine/shopping-habits.html

(4) D. R. George et al.   Dangers and Opportunities for Social Media in Medicine.  Clinical Obstetrics and Gynecology 56(3):453-462. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863578/

(5) P. Garrad et al. 2004.  The Effects of Very Early Alzheimer’s Disease on the Characteristics of Writing by a Renowned Author.  Brain 128(2);250-260.  http://brain.oxfordjournals.org/content/128/2/250

(6) R. Highfield. 2004.  Decline of Iris Murdoch… in her own words.  The Telegraph, 1 December 2004.  http://www.telegraph.co.uk/news/uknews/1477906/Decline-of-Iris-Murdoch…-in-her-own-words.html

(7) D. A. Snowdon et al. 1996. Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life: Findings from the Nun Study. Journal of the American Medical Association 275:528–532.

(8) P. Belluck. 2001.  Nuns Offer Clues to Alzheimer’s and Aging.  The New York Times, 7 May 2001.  http://www.nytimes.com/2001/05/07/us/nuns-offer-clues-to-alzheimer-s-and-aging.html

(9) J. A. Mortimer et al. 2005.  Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression.  Journal of Geriatric Psychiatry and Neurology 18(44):218-223.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1405917/

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