Synthetic Genetic Shakespeares

Examining the implications of science and technology


Synthetic Genetic Shakespeares

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

The Unilateralist’s Curse Meets the Biohacker Singularity

The resurrection of extinct horsepox virus using the tools of synthetic biology has generated controversy in the scientific community (1).  Gregory Lewis makes the case that this sequence of events provides a prime example of an under-considered peril posed by some biotechnology research – the unilateralist’s curse (1, 2).

It Only Takes One

The unilateralist’s curse may take effect when scientists make value judgments about whether to proceed with certain projects independently of one another.  Synthesizing horsepox virus could lead ultimately to improved smallpox vaccines.  However, the close relationship between horsepox and smallpox viruses arouses concerns that someone intent on doing harm might be able to use the newly published information as a blueprint for criminal action. 

Although I do not know the proportion of scientists opposed to the horsepox resurrection, for the purposes of discussion let’s imagine opinions break out this way; most researchers decline to undertake horsepox synthesis reasoning that improving a vaccine for a virus (smallpox) that has been extinct for nearly 40 years is not worth the effort or risk.  However, one (or a few groups) is convinced the endeavor has value and decides to perform the experiments and publish the results.  By going forward a small faction essentially overruled the majority consensus of their colleagues.  If the mavericks are correct and the project produces benefits, all is well.  But the curse comes into play if the well-intentioned mavericks have misjudged the situation and harm such as facilitating a terrorist attack with smallpox results.  The troubling aspect of the situation is an inherent bias to action – all that is needed to begin the cascade of events is a single dissident group or individual.  Provided everyone is able to gauge risks accurately and acts ethically, we are fine.

To be fair, the group performing the horsepox synthesis work probably did not knowingly violate a community consensus.  Scientific projects often involve comparatively small groups and with limited feedback from uninvolved colleagues.  That means researchers often make independent decisions about what projects to pursue and how to go about them. 

Institutional Safeguards

Several factors prevent the unilateralist’s curse from running rampant.  Researchers do not have a totally free hand to do anything because they are subject to several forms of institutional oversight.  Before work begins detailed research proposals must receive approval from Biosafety committees as well as Institutional Review Boards if the projects involve work with human subjects.  In addition, funding sources may have precise stipulations and strictures regarding what constitutes the allowed work scope and permissible activities.

Notwithstanding the possibility for error, misunderstanding and unforeseen circumstances that emerge in all human endeavors, the scientific community is probably going to manage itself responsibly.  What is there to worry about?        

The Unilateralist Singularity

The horsepox synthesis controversy illustrates how swiftly biotechnology is evolving.  What was a distant, hypothetical possibility 15 years ago is a published study today.  The tools have become better and cheaper, the expertise to use them has been disseminated widely and the biotechnology revolution is being democratized before our eyes.  More participation and knowledge will likely bring benefits.  And perhaps some challenges. 

Enter the biohacker, or the ultimate quirky unilateralist singularity.  Most will probably work responsibly and adopt the conventions of the professional research community.  However, we have seen some decidedly unconventional behaviors as individual biohackers have undertaken unilateral decisions to perform questionable actions (3, 4).  Will their peers deem these exploits as misguided, behavioral dead-end outliers?  Or are they the harbingers of a future where majority consensus regarding medical biotechnology intervention safety and efficacy is tyrannized by super-self-empowered individuals?  The issue is in doubt because even some members of the professional research community have had trouble making ethical choices regarding the use of new biotech-based therapies (5).  Hopefully, biohackers seeking role models will choose not to emulate regenerative medicine clinics selling dubious stem cell and other high-tech therapies to the desperate.

Rube Goldberg

Biohackers Beware

Biohackers seeking to achieve personal goals are virtually certain to rely on the published scientific literature to some degree.  However, they will be well advised to proceed with caution.  The scientific literature itself is intrinsically biased because of an emphasis on publishing positive results.  Is that astounding new study the final word or a statistical one-off fluke?  For anyone wanting to take an exciting result and leap into a clinical trial it might be good to keep in mind science is struggling with a reproducibility problem (6).  The biggest liars on our planet may not be politicians, but laboratory mice.  

Maybe it will turn out that key personal examples exert the greatest influence over biohackers and those who might wish to follow their lead.  For example, an article described how one young man seeking male enhancement had stem cells injected into his penis and indicated he felt the procedure was successful (4).  Although this outcome interpretation is questionable on several scientific grounds, maybe it will be enough to induce others to try the same thing.  Perhaps for this quest the unilateralist’s curse will be a sudden rise of terminal priapism cases. 

Update – March 10, 2018

A New York Times Sunday Review article by Pagan Kennedy reminds us (me) that self-experimentation on the basis of thin experimental evidence and peer emulation affect professional scientists.   

(1) Gregory Lewis.   Horsepox Synthesis: A Case of the Unilateralist’s Curse?  Bulletin of the Atomic Scientists, 19 February 2018.

(2) Nick Bostrom et al.   The Unilateralist’s Curse and the Case for a Principle of Conformity.  Social Epistemology 30(4):350-371.

(3) Sarah Zhang.   A Biohacker Regrets Publicly Injecting Himself with CRISPR.  The Atlantic, 20 February 2018.

(4) Kristen V. Brown.   This Guy Injected His Dick with Stem Cells to Try to Make It Bigger.  Gizmodo, 27 February 2018.

(5) Sheila Kaplan and Denise Grady.   F.D.A. Cracks Down on ‘Unscrupulous’ Stem Cell Clinics.  The New York Times, 28 August 2017.

(6) Monya Baker.   1,500 Scientists Lift the Lid on Reproducibility.  Nature, 25 May 1016.

(7) Chris Iliades.   Priapism is the Long-lasting Erection That You Really Don’t Want.  Find Out When and Why it’s a Medical Emergency.  Everyday Health.



The Big One

If Mary Shelley were writing Frankenstein today, Ian Haydon feels her astonishing tale would almost certainly involve synthetic biology (1).  Brilliant and conversant with the latest, highly provocative science of her day, it is easy to imagine she would recognize the far-reaching implications of this new capacity to re-engineer life.    

Is Frankenstein Still Relevant Today?

Written 200 years ago, this work still resonates as a disturbing cautionary tale.  Acknowledging an analogy between Victor Frankenstein’s macabre fictional endeavors and some of the goals of modern era synthetic biologists, Ian Haydon also draws some sharp contrasts.  Citing examples of highly accomplished scientists who are vocal advocates for the cautious use of new genetic manipulation technologies, he suggests this modern community of researchers embodies restraint and forethought.  A novelist seeking to craft a terrifying tale would find no modern day versions of Victor Frankenstein in this group of ethical luminaries.

As Above, So Below? 

Our true biotechnology story will be written by many participants holding diverse ideas about what is and is not permissible.  How will that play out?  We may have gotten a hint when a group of researchers announced they had resurrected an extinct relative of the smallpox virus using the tools of synthetic biology (2).  Not everyone viewed this development as positive (2).



Scientists exert control over their peers and have at times stepped back from the laboratory bench to examine ethical concerns before moving ahead with new research efforts (3).  However, imposing limits on controversial work areas has sometimes provoked bitter dissent and acrimony.  In one instance a researcher threatened to ignore restrictions (4), but later decided he would honor the terms set by colleagues and government officials.  Perhaps scientists lured by the potential of immense rewards, but stymied by guidelines they deem overly restrictive will one day deliberately defy their colleagues and violate community norms. 

A Predictable Future?

Sixteen years ago a group of scientists shocked their peers by showing it was possible to assemble a functional virus in a test tube using synthetic biology methods (5).  At that time the work, which took 3 years and quite a bit of labor to accomplish, provided a warning that the world was changing.  This proof-of-principle demonstration revealed many viruses could be built from scratch, prompting concerns about its use by bio-terrorists.  However, the virus synthesized (a poliovirus) was small and doing something horrendous with this technique like reconstituting smallpox was comfortably far out of reach – then.  Check the news, things have changed and we now face the prospect nefarious actors could build smallpox and other threatening agents far more quickly and easily (2).

In one general sense the future of synthetic biology technology is simple to predict; democratization and dissemination.  More scientists in more places around the world will have access to ever more powerful, easy-to-use biotechnology tools.  Take a look at CRISPR gene editing.  In a stunningly short period, CRISPR genetic editing has become a routinely used method in many labs.  Like to get into that area yourself?  You can buy CRISPR editing kits online and jump right into this burgeoning field. 

Pursuing Big Dreams

Developments with CRISPR engineering are coming so quickly it is impossible to keep up with them.  Talented and empowered scientists will employ these tools in ways that are impossible to foresee, but it seems safe to bet democratization and dissemination will yield enormous benefits. For the most part we have good reason to believe scientists will work carefully with these new tools. 

We have some hints there may be more to this story than what scientists choose to do with emerging biotechnologies (6).  As capabilities have dispersed beyond the borders of the traditional scientific and biomedical research communities, we have already seen biohackers employ them in some unconventional ways.  For example, how may stem cells benefit humanity?  The claim that one person has employed them in pursuit of male enhancement (7) suggests that human ingenuity is about to lead us down some quirky roads. 

As biotechnology evolves and scatters over the world, the centuries-old message of Frankenstein may be relevant to more people than ever.  If it goes unheeded, the modern day real life incarnations of Victor Frankenstein chasing their eccentric dreams may learn some hard lessons.    


(1) Ian Haydon.   Bioengineers Today Emphasize the Crucial Ingredient Dr. Frankenstein Forgot – Responsibility.  The Conversation, 5 March 2018.

 (2) Kai Kuperschmidt.   A Paper Showing How to Make a Smallpox Cousin Just Got Published. Critics Wonder Why.  Science, 19 January 2018.

(3) David Baltimore et al.   A Prudent Path Forward for Genomic Engineering and Germline Gene Modification.  Science 348(6230):36-38.

(4) Declan Butler.   2012.  Mutant-flu Researcher Plans to Publish Without Permission.  Nature, 17 April 2012.

(5) Andrew Pollack.   Traces of Terror: The Science; Scientists Create a Live Polio Virus.  The New York Times, 12 July 2002.

 (6) Sarah Zhang.   A Biohacker Regrets Publicly Injecting Himself With CRISPR.  The Atlantic, 20 February 2018.

(7) Kristen V. Brown.   This Guy Injected His Dick With Stem Cells to Try to Make It Bigger.  Gizmodo, 27 February 2018.




Will We Forget You, Flu?

When it comes to the flu, each year is a different story.  By all objective measures, the 2017-18 influenza season has definitely been a bad one (1).  The chief public health measure used to control influenza is wide-scale immunization.  And this season the chief – and valid – complaint about the flu vaccines is that they provided weak protection.    


Making Flu Vaccines – It’s Not So Simple

In an age of medical miracles, why can’t someone produce an effective flu vaccine?  The first problem is that influenza never attacks alone.  Every year several distinct types and multiple subtypes of flu viruses (2) will be in general circulation.  The seasonal flu vaccines are formulated to protect us against 3 or 4 viruses.  Unfortunately, it is not possible to cover all the existing viruses or new variant forms that inevitably crop up and spread during flu season.  Until someone devises a ‘universal’ flu vaccine (3) some gaps will remain. 

Another problem has to do with time requirements to produce vaccines and the fact that success hinges on making accurate predictions about an erratic foe.  Today vaccine components are mostly produced in embryonated chicken eggs.  The complete process is lengthy because it takes a great deal of time to orchestrate the egg supply and produce enough viral antigens.  That means if a vaccine does not perform well we are usually stuck with it for the season.  But there is an additional wrinkle to this problem.  Let’s imagine producers make a vaccine that provides perfect protection against the viruses creating havoc at that specific moment in time.  That does not mean influenza has been vanquished.  Because flu viruses evolve quickly and constantly, there is a high probability even a perfect vaccine will fail to provide full protection in only a few months.  Unlike other vaccines for disease agents such as measles or chickenpox, what worked last year may not – likely will not – work well for the next flu season.  The intrinsic variability and long vaccine production lead times forces vaccine manufacturers to decide (guess) 6 months or more in advance which flu viruses will create the biggest problems in the next flu season.  Incorrect assessments can leave us with vaccines that match up poorly against the viruses actually in circulation.  Remember, vaccine manufacturers are attempting to predict the future for up to 4 distinct and highly variable flu viruses – one mistake can ruin a lot of otherwise superb work.  In addition, during the extended time periods necessary to scale up flu vaccine manufacture, the viruses attacking humans will undergo continuous diversification.  These incessant changes virtually guarantee vaccines and flu viruses will generally have some degree of mismatch. 

There is another factor affecting vaccine success – influenza viruses grown in chicken eggs become acclimated to those unique environmental conditions.  To be a good vaccine stock for most production methods, the influenza viruses must grow avidly in chicken eggs.  Unfortunately, egg-adapted viruses may not be precise matches to the viruses being spread by respiratory infection of human beings.  New vaccine production methods employing cell cultures may shorten the time requirements for vaccine production and make mass-scale production easier.  In addition, claims have been made that the cell-based vaccine stocks yield viruses that do not sport mutations that often emerge in egg-cultured strains and are anticipated to match more reliably the forms in actual circulation (2).  However, these influenza vaccine strains are still grown in living cells which suggests some adaptation to the new host environment is inevitable.  This year the A H3N2 viruses were most problematic and it will be interesting to determine whether the products from cell cultures offered superior protection to those using traditional chicken egg methods.  Perhaps DNA-based vaccines (3) will solve both the adaptation and mass production problems for future influenza vaccine producers.

Fostering Problems

Influenza has been with us for a long time, but the human condition is changing in ways that may elevate the risk for pandemics.  Populations are growing and crowding into larger cities and megacities of 10 million or more inhabitants.  Massing so many persons in close proximity may promote the amplification and rapid spread of influenza as well as other diseases. 

Steadily expanding populations have placed accelerating demands on the food supply.  The adoption of large-scale production strategies provides high quality food at low costs, but analogous to the situation with megacities, efficient animal husbandry methods may pose enhanced infectious disease transmission threats.  Important food animals such as chickens and pigs are also reservoirs for influenza viruses, many not currently known to circulate in humans.  We are not going to eliminate the need for these animals which means we will have to be diligent about reducing risks for disease agent transmission between livestock, human caretakers and production workers.  For example, producers and government investigators devote a great deal of effort to detect and eliminate avian influenza viruses thought to possess potential to spark a pandemic as soon as they are discovered in food animals (4, 5). 

Jason Wiebers Farms 2


But what if exotic avian influenza viruses only kill some chickens?  Aside from the huge economic losses to producers and taxpayers, under the right circumstances the medical consequences could be devastating because many human vaccines are produced in chicken eggs.  An avian influenza outbreak in vaccine egg production facilities could mean that even an ‘average’ flu season would produce far more human deaths than normal.  In a situation like that it is unrealistic to believe manufacturers of anti-influenza drugs like Tamiflu would be able to keep up with the demand surge.   

Egg flu                                         

Forget About It

Influenza is in the news and public consciousness at the moment because this season has been long and tough.  The data suggests the U.S. epidemic has peaked (1) and soon the numbers of afflicted patients jamming Emergency Departments will decline quickly.  That’s when we will do what we always do with the flu – forget about it.  Most of us will probably think nothing more of influenza until next October when we receive reminders to get our seasonal flu vaccination.  Maybe we will heed them.

Flu2018 season


Influenza is not the only disease we ‘manage’ this way – severe, acute respiratory syndrome (SARS) and Ebola outbreaks consumed our attention and then faded away.  Unfortunately, declining public attention goes hand-in-hand with vanishing political will and resources necessary to prevent future outbreaks. 

Flu trends

The graph above confirms that flu outbreaks come at different times and exhibit different degrees of severity.  However, influenza remains completely predictable in one critical way – descendants of the viruses will return next year.  Apart from that it is nearly impossible to assert with confidence whether the next encounter will be mild or nasty.  Maybe one migrating duck will bring a new virus that devastates chickens or something dangerous will bubble out of a megacity, perhaps to unleash a pandemic as deadly as the 1918 killer flu.  We will know when it emerges. 

Researchers have developed several new types of influenza preventative vaccines to improve efficacy and coverage.  New vaccine production methods that may shorten lead times or yield superior products are being tested.  Public concern about the flu will naturally fade as cases and news coverage decline.  However, we will be wise to not forget about influenza completely and demand resources are available to improve our ability to combat this unrelenting threat to human health.  Ready or not, the flu will be back.  


(1) Donald G. McNeil, Jr.   This Flu Season is Now the Worst in Years. Here’s Why.  The New York Times, 18 January 2018 (updated 16 February 2018).

(2) Centers for Disease Control and Prevention. Frequently Asked Flu Questions for the 2017-2018 Influenza Season.

(3) Merika T. Koday et al.   Multigenic DNA Vaccine Induces Protective Cross-reactive T Cell Responses Against Heterologous Influenza Viruses in Nonhuman Primates.  PLoS One, 21 December 2017.

(4) Anne Trafton.   Tracking the Spread of Bird Flu.  MIT News, 17 March 2017.

(5) Donald G. McNeil, Jr.   Bird Flu is Spreading in Asia, Experts (Quietly) Warn.  The New York Times, 17 November 2017.


Are Scientists Putting Cryptic Messages in Their Papers?

Appropriate for Valentine’s Day, the editors of the prestigious scientific journal, Nature, wrote about marriage proposals embedded within scientific publications (1).  As scientists are inclined to do, the pros and cons of this strategy were examined. 

After some lighthearted exposition the editors go on to ponder heavier issues of surreptitious messages in scientific publication acknowledgements and main contents sections along with offering some examples of authorship credit funny business.  The bottom line viewpoint of the Nature editorial board regarding such activities is drawn clearly – potential contributors incubating notions to convey personal messages are admonished to cease and desist immediately.

Outside of acknowledgements sections which generally allow expressions of thanks, dedications/remembrances, etc. by authors, how frequently have personal messages been embedded directly within scientific publications contents?  The Nature editors are uncertain how many instances may be present on their pages, but clearly are compelled to proactively ensure the integrity of their products.  Perhaps the readership will now scour the journal archives for examples or culprits will come forward to showcase their efforts.  Notwithstanding the marriage proposals and whimsy sometimes placed in acknowledgements, it may be important to recognize the scientific enterprise can be frustrating.  Perhaps some, or many, scientists disgusted by the trials and tribulations of funding and publishing have devised imaginative ways to strike back.


It will be interesting to see if and how deeply this onion can be peeled.  We are talking about highly creative people, so there is a prospect we might be treated to some truly novel, hidden-in-plain-sight messages.  Scrutinizing scientific publications for veiled communications may have some unintended ramifications such as energizing conspiracy theory buffs.  Could this lead to a History Channel series seeking evidence of a modern obscurantist incarnation of the Illuminati?  Maybe we should anticipate a few new items will be added to the instructions for authors. 


(1) The Editorial Board.   From Proposals to Snarks: The Messages That Scientists Sneak Into Their Papers.  Nature, 14 February 2018.


Mars Draws Near

Making its closest approach to Earth since 2003, the planet Mars will put on quite a show this summer (1).  The red planet will trek eastward and then loop backwards against the background of fixed stars, becoming steadily brighter as the distance from us shrinks (2).  During this journey Mars will take on a color reminiscent of a luminous blood drop making it easy to see why ancient Roman and Greek observers associated this planet with their gods of war, Mars and Ares.


The realization that Mars was somewhat similar to our Earth and a close neighbor by astronomical standards has inspired interest and speculation in the general public as well as the scientific community.  Much of the fascination and research has involved the prospect that Mars might harbor life.  Over the centuries, scientific opinions on the prospects for life in our solar system have changed often as a consequence of new information gleaned with the use of improved technologies and instruments.  Percival Lowell amassed visual telescopic observations and deduced from them he had glimpsed the evidence of global environmental/climate change and a planetary-scale engineering project.  However, Lowell’s ideas were controversial from top to bottom and his 1908 book, Mars as the Abode of Life, was critiqued as a pseudoscientific bamboozling of a trusting public (3), the fake news of its day.  Fifty years later investigators combining visual evidence with spectroscopic analyses posited large parts of Mars must be vegetated (4).  These ideas were challenged and reinterpreted, but probably few things changed public perceptions more than the Mariner spacecraft missions which provided close-up views of a decidedly desolate looking planet. 

Mars (2)


Advanced civilizations and expansive, living forests have been ruled out, but exploration and the search for evidence of life on Mars has continued.  Today, as a number of clever commentators have noted, Mars is the first planet we know to be inhabited by active robots from another world.  Mars remains a high priority target for scientific researchers and organizations proposing to colonize it.  It will be interesting to see how the demands of the various groups vying to conduct operations on Mars will be managed.

Mars rover            

No special equipment will be necessary to observe this celestial spectacle and you can start following events immediately (2).  Right now (February, 2018) at dawn Mars is in the southern sky in the constellation of Scorpius.  This is a good time to see the planet fairly near the red giant star Antares, the heart of the scorpion and the ‘rival’ of Mars (5).  To my eye, their magnitudes are well matched currently, but watch as Mars moves and changes in brightness and deepens in color.  During the summer months when Mars is closest, persons in the Northern hemisphere should look low in the southern sky during the evening hours.  For those with telescopes, this summer will be a prime time to train them on Mars.  Truly close approaches like this occur only at 15-17 year intervals when even modestly-sized instruments will reveal polar ice caps, dark surface markings, clouds and perhaps gigantic dust storms.

(1) Deborah Byrd.   Mars Brighter in 2018 Than Since 2003., 8 February 2018.

(2) Martin J. Powell. The Mars Apparition of 2017-2019.  Naked Eye

(3) Eliot Blackwelder.   Mars as the Abode of Life (review of the book written by Percival Lowell). Science 29:659-661.

(4) William M. Sinton.   Further Evidence of Vegetation on Mars.  Science 130:1234-1237.

(5) Elizabeth Howell.   Antares: Red Star at the End of its Life., 17 August 2017.


We Come Into the World Alone – Sort Of


Speculations About Artificial Womb Technology

Ideas about how humans and other animals interact with the microbial world are undergoing some big revisions.  Multiple lines of evidence reveal an organism’s microbiome does far more than promote food digestion, but is an essential – and extensive – symbiosis.  Investigators are now tracing the multifaceted interactions between host and microbial flora that affect development, organ structure and perhaps behavior (1).  The internal and external surfaces of animals are unique, environmentally sensitive ecosystems.  One of the more radical ideas to come forth recently is that humans might acquire billions of bacterial viruses (bacteriophages) from food and water daily (2).    This interplay has unknown consequences for both the resident bacterial flora and the host.

Mircobes of yore


Are We Ever Sterile?

The bacterial flora of humans changes with chronological age and responds to environmental inputs.  A general belief that the womb was normally sterile led to the assumption that the colonization processes only began with passage through the birth canal.  New findings suggest that the charter members of our microbial teams might take their places during gestation as bacteria are passed from mother to the developing child (3). 

The hypothesis human microbial communities are founded before birth is controversial because the direct experimental evidence is equivocal (3).  Does the existence of germ-free (gnotobiotic) animals rule out the gestational establishment model?  It does complicate the idea, but this objection may conflate two rather distinct situations.  Observations suggest the interplay between microbial ecosystems and host could be much more dynamic than suspected previously (2).  Further, transient bacteremia – bacteria in the blood – is common in persons of normal health; temporary surges of microbes in the circulatory system follow activities such as tooth brushing.  Could transient invasions play a role in fetal development or the training/priming of the forming immune system?  We know some pathogens are adept invaders and able to persist within host cells for decades.  Could communities be established in utero by hardy pioneer microbes that are difficult to culture or present in low numbers?                 

The Hygiene Hypothesis

Another idea that has gained currency recently is that our modern era quest toward cleanliness and wide use of antibiotics has backfired.  Taking sanitation of our surroundings and ourselves too far has impeded our innate defenses by antagonizing the normal microbial communities needed to train and maintain our immune systems (4).  The results may have been upsurges in autoimmune diseases like asthma, food poisoning susceptibility and perhaps obesity (4).  The hygiene hypothesis is an economical way to account for the rise of allergies and degenerative diseases.  However, it is important to recognize many factors have changed over the last decades including diet, life styles and exposures to chemicals such as antibiotics.  That makes it hard to decide which is(are) a preeminent or even a significant influence on overall health status.    

Meet You at the Crossroads – Reproductive Cloning, Mammophants and Artificial Wombs

The announcement the reproductive cloning of nonhuman primates has been achieved reminds us that this basic strategy has succeeded with a number of animal species (5).  Scientists are speculating that a confluence of advances might turn fanciful dreams like resurrection cloning of extinct species such as the woolly mammoth into reality (6).  Developments in artificial womb technology – ectogenesis – may be a key facet in furthering such work and more (6, 7). 

We are rapidly approaching a point where the traditional norms and strictures of biomedical research with embryos and ectogenesis technology will be splintered (The Rules No Longer Apply ).  How well will efforts like resurrection cloning mammophants, the term coined to describe these strange hybrid beasts with no natural progenitor kin, succeed (6)?  In one sense, if it all works, it will be eerily reminiscent of the Frankenstein tale written by Mary Shelley two centuries ago.  But, could it be that artificial wombs will just plain turn out to be too sterile?  Might those who would breathe new life into extinct creatures through ectogenesis technology fall victim to an unforeseen issue?  Perhaps the uterine hygiene hypothesis will be confirmed if and when the unleashed beasts from artificial wombs have immune dysfunction or other developmental issues.  Instead of being an ingenious solution to tundra melting the first resurrected mammophants might be the animal equivalents of hot house flowers that just do not do well in nature. 


It will be interesting to see how our technological dreams play out in the real world. 

(1) Sarah C. P. Williams.   Gnotobiotics.  Proceedings of the National Academy of Sciences of the United States of America. 111(5):1661.

(2) Giorgia Guglielmi.   Does a Sea of Viruses Inside Our Body Keep Us Healthy?  Science, 21 November 2017.

(3) Cassandra Willyard.   Could Baby’s First Bacteria Take Root Before Birth?  Nature, 17 January 2018.

(4) Kate Murphy.   Invite Some Germs to Dinner.  The New York Times, 9 May 2015.

(5) Gina Kolata.  Yes, They’ve Cloned Monkeys in China. That Doesn’t Mean You’re Next.  The New York Times, 24 January 2018.

(6) Hannah Devlin.   Woolly Mammoth on Verge of Resurrection, Scientists Reveal.  The Guardian, 16 February 2017.

(7) David Warmflash.   Artificial Wombs: The Coming Era of Motherless Births?  Genetic Literacy Project, 12 June 2015.



Do Despots Dream of Cloned Kids?

The news nonhuman primates have been cloned captivated public attention (1, 2).  In spite of the fact that this achievement was challenging and, currently, cannot be used to reproduce adults (3), discussions naturally veered into speculations about cloning human beings (2).  Notions of human reproductive cloning have been generally discouraged by the scientific community, but such work is not explicitly outlawed everywhere.  Science journalist Gina Kolata writing in The New York Times (3) offers a blunt assessment of the situation – such efforts will not involve any of us.  I believe her prediction is correct although probably for a different reason.

Leaving a Mark

Many of us are driven to leave our mark on the world in some way through creative endeavors, building projects or successful business enterprises.  The ways are many, but the purpose is simple; leaving something on this cold, indifferent world that will outlast your living tenure.  For most of us this may be accomplished through having a family and a grave marker.  Just as headstones and tombs come in a variety of forms, others seek grander demonstrations.



The New, High-Tech Royalty?

Not since the Gilded Age have successful and wealthy entrepreneurs exerted such overt influence over our culture.  The benefits to society have been tremendous and the ambitions of certain super-empowered plutocrats now extend to the stars.  A bit like the Pharaohs erecting larger pyramids or monarchs determined to have the finest palaces, all credit to these modern day movers and shakers for seizing the opportunity to accomplish their outsized dreams.

Perhaps performing amazing feats like exploring Mars will finally satisfy the deep needs to leave a lasting legacy.  However, maybe some persons feeling the urge to persist through time will soon find a new technological means to do it.  If you deem yourself the most marvelous gift to humankind ever, reproductive cloning will enable you to keep on giving the awesome gift of you forever.  Indeed, under some circumstances in which the authority to rule a nation is passed to succeeding offspring, reproductive cloning might become the ultimate political power tool.  Royal lineage is so yesterday.

Genuine Imitation, the Next Best Thing to Immortality?

Human beings have already been cloned by Mother Nature – we know them as identical twins.  Essentially genetically identical, twins share a large number of traits, but not quite exactly everything.  They are also completely autonomous beings.  From the perspective of persons seeking to clone themselves, the net sensation may be most akin to being the parent of your own twin.  Will that creature be like you?  This might be a good time to review The Boys From Brazil by Ira Levin. 

The inevitable perfection of reproductive cloning techniques means the Despot’s dream of ensuring secure inter-generation passages of power will be achieved in perpetuity.  Even if the clones fall a bit short in some ways, it’s still a less risky prospect than making heirs-to-power the old-fashioned way.  Human reproductive cloning may be discouraged, but it is not illegal everywhere.  These genuine imitations may not quite be equivalent to immortality, but a capacity to create them may serve particular needs.  Someone, somewhere will attempt to fulfill that dream sometime.                 

So, is Ms. Kolata’s prediction about human reproductive cloning correct?  Most probably it will not involve you.  Reproductive cloning will not be for the little people.

(1) Dennis Normile.   These Monkey Twins Are the First Primate Clones Made by the Method that Developed Dolly.  Science, 24 January 2018.

(2) David Cyranoski.   First Monkeys Cloned with Technique that Made Dolly the Sheep.  Nature, 24 January 2018.

(3) Gina Kolata.   Yes, They Cloned Monkeys in China.  That Doesn’t Mean You’re Next.  The New York Times, 24 January 2018.


For a unique discussion of the implications of human reproductive cloning, including clone insurance, listen to this episode of The Ozone Nightmare with Joe and Lando

Red Sky at Morning

The Evolution and Dissemination of Biotechnology

A scientific paper demonstrating the molecular resurrection of extinct horsepox virus (1) generated controversy six months before it had been formally published in a scientific journal (2).  And once it appeared, disputes over the fundamental rationale (3) for the work and its possible biosecurity implications reignited immediately (4, 5).  The scientists performing this work aimed to create more effective smallpox vaccines.  Their critics declared the work unnecessary and fret the detailed methodological descriptions could serve as a convenient practical guide for others who might attempt the same thing with the human smallpox virus (2).  A representative for the journal revealed a committee on ‘dual use’ research such as this horsepox study concluded publication was warranted.  However, other scientists had appealed directly to the editor to decline to publish the work or felt that additional approvals by national and/or global health authorities were needed before the article should have been released into the public domain (2). 

A Wake-up Call? 

The horsepox project was approved by the Canadian federal government (5).  Will the resulting turmoil serve as a “wake-up call for science agencies and governments” as one expert put it (2)?  The truth is it seems some of the authorities have been hitting the snooze button for decades.  The horsepox dispute is the latest in a series of battles, many of them pitched, protracted and public (2). 

The idea some biological research might pose risks to the public health and safety received official affirmation with the publication of what is commonly known as the ‘Fink Report,’ named after Dr. Gerald Fink, the chair of a National Research Council committee charged to examine the issue (6).  The scientific peer review process and the need to assess risks vs. benefits of the open publication of results were identified as key areas of concern 15 years ago (7).  Since that time the scientific community has been roiled by clashes over the wisdom of reconstructing the 1918 killer influenza (8) and whether to proceed with gain-of-function experiments using agents such as H5N1 bird flu (2).

Squeezed by Dual Dilemmas

Few things reveal how quickly biotechnology is evolving than the horsepox virus resurrection controversy. (Vanishing Point)  Those charged with ensuring dual use research does not create undue hazards are facing a double dilemma of their own; swiftly advancing technology is colliding with the traditional ways of publishing results.  Researchers can now take long-published genomic sequence data and use it to achieve what only a decade ago was utterly impossible.  It can no longer be taken for granted that some exploits will remain unattainable indefinitely.  Safeguarding methods and perhaps restricting some data to persons with a demonstrated need-to-know may now be necessary.  Today the swift penetration of technology of unprecedented power into routine use worldwide means new shocks might come from anywhere.  Dr. Michael Osterholm, a leading authority on biosecurity concerns and public policy, reacting to the preliminary reports of horsepox resurrection, summed it up succinctly,

            “We never thought or expected it to come from a place like Alberta.” (2)     




A direct ramification of that concern is that the horsepox virus resurrection work was done at a place that is not generally recognized as center for microbiology and synthetic biology (2).  The potential of capable scientists worldwide to conduct quality work is being amplified immensely and democratically by advancing biotechnology.      

The Role of Private Enterprise

The resurrection of horsepox virus was funded through a contract with a pharmaceutical company which built on a legacy of prior support from the Canadian government (3).  The situation is likely to unleash a debate as to how to oversee and manage privately-funded research.  Analogous to the situation with the wake-up calls that went unheeded, explicit concerns over the expanding significance of corporate influences (9) seem to have made few research policy inroads.

An Unpredictable Future

In 2003, a White House Office of Science and Technology Policy official offered an opinion that the scientific community had limited time to resolve these issues, noting that controversial papers might induce public demands for government action.  Over the years since that prediction, more controversies have erupted, and some new rules have been implemented.  All the while the dissemination of new biotechnological capabilities has accelerated.  Unless scientists are willing to acknowledge that evolving situations demand changes in how information is secured the next step in the process may not be driven by another controversy, but a catastrophe.

(1) S. Noyce et al. 2018.  Construction of an Infectious Horsepox Virus Vaccine From Chemically Synthesized DNA Fragments.  PLoS One 13(1): e0188453.

(2) Joel Achenbach and Lena H. Sun.   Scientists Have Recreated an Extinct Poxvirus in the Lab.  But Don’t Freak Out.  The Washington Post, 8 July 2017.

(3) University of Alberta Faculty of Medicine & Dentistry. Creation of synthetic horsepox virus could lead to more effective smallpox vaccine: Synthetic technology breakthrough points to safer vaccines and targeted cancer treatments. ScienceDaily, 19 January 2018.

(4) Kai Kupferschmidt.   Critics See Only Risks, No Benefits in Horsepox Paper.  Science 359(6374):375-376, 26 January 2018.

(5) Stephanie Soucheray.   Step-by-step Horsepox Study Stokes Dual-use Controversy.  CIDRAP News, 23 January 2018.


(7) Erika Check.   U.S. Officials Urge Biologists to Vet Publications for Bioterror Risk.  Nature 421:197

(8) Donald G. McNeil, Jr.   Bird flu paper is Published After Debate.  The New York Times, 21 June 2012.

(9) Paul Berg.   Meetings That Changed the World: Asilomar 1975: DNA Modification Secured.  Nature 455:290-291.


“Because It Is There”


Pushing the Limits of Science and Medicine

Asked why he wanted to scale Mount Everest, George Mallory’s response was memorable: “Because it is there” (1).  He and his partner, Andrew Irvine, died trying, possibly only a few hundred meters or less below the summit.


That fundamentally human drive to accomplish the (formerly) un-achievable still exists.  You may have sensed it in the news reports about scientists and technologists performing attention-grabbing feats.  We certainly live in a time when once insurmountable barriers and red lines seem to be crossed frequently.

Questioning Rationales

The main goals of scientific research are usually clear.  However, several recent exploits have provoked a barrage of questions from both the general public and the scientific community about why the works were performed in the first place.  Will publication of methods used to re-create a probably extinct horsepox virus help create a safer smallpox vaccine or is the paper a blueprint for (hypothetical) mal-intentioned actors to bring back a deadly disease scourge (2, Vanishing Point )?  Was the demonstration of a 3-parent baby technique about helping people with mitochondrial genetic mutations have children of their own or developing better, potentially more lucrative, fertility treatments (3, Green Lights or Greener Pastures for ‘3-Parent’ Baby Clinical Trials? )?  With the announcement of the cloning of primates (4, 5, 6), the continuous drumbeat of biomedical barrier breaching goes on.

Why did someone create Monkey Deux? 

The basic method was demonstrated by Sir Ian Wilmut and collaborators when they produced Dolly, the cloned sheep.  In the over 20 years since that event the approach has been extended to a wide range of other animals (4). However, the news accounts reveal cloning primates required a great deal more effort than copying what had been done to obtain Dolly (4, 5, 6).  The scientists who eventually cloned macaque monkeys aimed to develop a means to produce genetically-identical individuals to facilitate modeling of complex human diseases (6).  Such animals would offer several technical advantages and may be especially useful in pre-clinical assessments of new therapies, but it is unclear whether all scientists will embrace their adoption (5).         

What comes next? 

At this point the journalistic consensus is that the reproductive cloning of human beings is not imminent.  First, the current methods do not work with genetic materials harvested from adult cells (4) and ethical strictures apply to such undertakings.  However, the latest success with nonhuman primates has implications for therapeutic cloning efforts (7) to create cells which might prove useful in regenerative medicine (8).  In fact, when it comes to the basic technique, reproductive and therapeutic cloning methods are essentially the same (8).  Therapeutic cloning work will build on the new knowledge acquired from continued experiments to perfect the reproductive cloning of nonhuman primates.  

Developing primate clones for biomedical research and efforts to perfect therapeutic cloning may yield important benefits.  As new knowledge and capabilities mount, how long will it be before serious attempts to perform reproductive cloning of human beings are attempted?  The idea is clearly attractive to some (9) suggesting persons with sufficient private resources will eventually devise ways to pursue their egomaniacal visions.  It may come down to finding someone determined to be the first person to scale that scientific mountain.   

(1) James M. Clash. “Because it’s there.”  Forbes, 29 October 2001.

(2) Kai Kuperschmidt.   A Paper Showing How to Make a Smallpox Cousin Just Got Published. Critics Wonder Why.  Science, 19 January 2018.

(3) Andy Coghlan.   Exclusive: ‘3-Parent’ Baby Method Already Used for Infertility.  New Scientist, 10 October 2016.

(4) Gina Kolata.   Yes, They Cloned Monkeys in China.  That Doesn’t Mean You’re Next.  The New York Times, 24 January 2018.

(5) Dennis Normile.   These Monkey Twins Are the First Primate Clones Made by the Method that Developed Dolly.  Science, 24 January 2018.

(6) David Cyranoski.   First Monkeys Cloned with Technique that Made Dolly the Sheep.  Nature, 24 January 2018.

(7) Michell L. Sparman et al.   International Journal of Developmental Biology 54(11-12):1671-1678.

(8) Charlotte Kfoury.   Therapeutic Cloning: Promises and Issues.  McGill Journal of Medicine 10(2):112-120.

(9) Emma Young.   First Cloned Baby Born on 26 December.  New Scientist, 27 December 2002.




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