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Synthetic Genetic Shakespeares

Examining the implications of science and technology

Did Scientists Taking Untested Vaccines Shoot Themselves in the Foot?

Did the COVID-19 pandemic begin with a laboratory leak? Controversy rages as scientists and government officials battle to reach an evidence-based answer to that question (1). Whether or not SARS-CoV-2 eluded control, reviews of high-containment laboratory facility operations worldwide are warranted to minimize the risks a future disaster could emerge from one of them (2).

A Conspiracy Theory Hothouse

Whether knowledge acquired through conducting gain-of-function (GOF) experiments to make pathogenic viruses more virulent justifies the potential risks has divided scientists for over a decade (1-3). Unfortunately, the processes used to evaluate GOF research funding proposals and approve release of scientific journal publications produced by that support have been criticized for coverage gaps and lack of transparency (4-6). Rising public apprehensions about research on dangerous viruses combined with long-simmering, public disputes over GOF research oversight emanating from the scientific upper echelons make the area a ripe target for misinformation propagators and conspiracy theorists.                    

Violating Public Trust

The public trusts that the scientific research we support will be conducted safely and ethically. Scientific research has yielded enormous benefits to society such as novel vaccines able to halt the COVID-19 pandemic produced in record-breaking short time frames. Notwithstanding the spectacular successes in combatting this terrible pandemic, anyone seeking to cast the scientific enterprise in an unfavorable light can mine published articles to find plenty of grist for their personal mills. For example, one researcher conducting GOF work on avian influenza viruses made particularly intemperate statements to a science journalist regarding his intention to publish results without required government approvals (7). Another researcher defied federal regulations to conduct a field experiment using genetically modified bacteria in an action he characterized as a deliberate act of “civil disobedience” (8). Arrogating authority to act contrary to rules and regulations is a superb way to destroy public confidence in scientists.         

Clearly, some scientists can be impatient and unreasonable. The D.I.Y. coronavirus vaccine situation (9, 10) offers a more recent and troubling example of ill-considered actions. Groups of scientists convinced they had a solution to the urgent coronavirus pandemic threat, began administering untested and unvalidated vaccine preparations to themselves. These are people who understand the processes of safety and efficacy testing and presumably were cognizant of the risks. In principle, if they used private funding sources and something went awry or the vaccine was simply impotent, they hurt only themselves, so no harm, no foul?

Image Confronts Reality – A Problem of Public Perception

The fact that multiple scientists skipped long-established safety and efficacy testing protocols in the service of their personal fears/needs is a little troubling. We are not talking about one or two rogue actors and that invites questions about just how many scientists might be/are situational rule benders. For example, do most researchers working in high-containment laboratory facilities dutifully follow all the operational rules of conduct or do they cut corners on any they deem inconvenient or view as useless bureaucratic overkill? In the event of laboratory mishap, should we trust them to report what transpired accurately or might they shade the truth? It is unfair to judge all by the actions of a few, but clear that the strange D.I.Y. vaccine situation and its implications provides a ready-made cudgel to bash the entire scientific enterprise. 

GOF research and the safety of high-containment laboratory facilities are about to be subjected to intense public scrutiny. Hopefully, the questionable norm-bending actions of frightened or overconfident scientists will not end up shooting all of their colleagues in the foot. 

(1) Jorge Casesmeiro Roger. 2021. By Investigating Itself, the US Can Answer Many of the Key COVID19 Origin Questions. Independent Science News, 8 June 2021. https://www.independentsciencenews.org/commentaries/by-investigating-itself-the-us-can-answer-many-of-the-key-covid19-origin-questions/

(2) Laura H. Kahn. 2021. How to Make Biomedical Research (and Biosafety Labs) Less Dangerous and More Ethical, Post-COVID-19. Bulletin of the Atomic Scientists, 8 June 2021. https://thebulletin.org/2021/06/how-to-make-biomedical-research-and-biosafety-labs-less-dangerous-and-more-ethical-post-covid-19/#.YMIkLUqGH7o.twitter

(3) Donald G. McNeil, Jr. A Federal Ban on Making Lethal Viruses is Lifted. The New York Times, 19 December 2017. https://www.nytimes.com/2017/12/19/health/lethal-viruses-nih.html?_r=0  

(4) Ed Yong. 2012. Why Did a U.S. Advisory Board Reverse Its Stance on Publishing Mutant Flu Papers? National Geographic, 2 April 2012. https://www.nationalgeographic.com/science/article/why-did-a-us-advisory-board-reverse-its-stance-on-publishing-mutant-flu-papers

(5) Lynn C. Klotz and Gregory D. Koblentz. 2018. New Pathogen Rules: Gain of Function, Loss of Clarity. Bulletin of the Atomic Scientists, 26 February 2018. https://thebulletin.org/2018/02/new-pathogen-research-rules-gain-of-function-loss-of-clarity/

(6) Jocelyn Kaiser. 2020. After Criticism, Federal Officials to Revisit Policy for Reviewing Risky Virus Experiments. Science, 24 January 2020. https://www.sciencemag.org/news/2020/01/after-criticism-federal-officials-revisit-policy-reviewing-risky-virus-experiments

(7) Declan Butler. 2012. Mutant-Flu Researcher Plans to Publish Even Without Permission. Nature, 17 April 2012. https://www.nature.com/articles/nature.2012.10469

(8) Keith Schneider. 1987. Tearful Scientist Halts Gene Test. The New York Times, 4 September 1987. https://www.nytimes.com/1987/09/04/us/tearful-scientist-halts-gene-test.html

(9) Antonio Regalado. 2020. Some Scientists are Taking a DIY Vaccine, and Nobody Knows if it’s Legal or if it Works. MIT Technology Review, 29 July 2020.  https://www.technologyreview.com/2020/07/29/1005720/george-church-diy-coronavirus-vaccine/

(10) Heather Murphy. 2020. These Scientists Are Giving Themselves D.I.Y. Coronavirus Vaccines. The New York Times, 1 September 2020. https://www.nytimes.com/2020/09/01/science/covid-19-vaccine-diy.html

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Featured post

Down to Earth – The First Mars Sample Return Mission

The detailed planning process has begun for a future NASA mission to transport small rock and dirt samples from Mars to Earth. Long imagined, this formidable task with the promise of an enormous scientific payoff is at last on the way toward finally being underway (1).    

That NASA engineers will devise a technologically dazzling plan to achieve the ambitious mission goals is certain. However, getting Mars samples to Earth is only the beginning of this effort. 

Safeguarding Planets

Do soils and rocks on the surface of Mars harbor any living organisms? Opinions vary (1, 2). Evidence suggests Mars was wetter and warmer in the distant past, perhaps life once flourished there. If that is true, what happened to it as conditions changed? If the consensus of the scientific community is that samples collected at the Martian surface are unlikely to harbor any viable microbes or the hardy analogs of spores, is it OK to put aside worries over back-contamination of Earth? Whether the hypothesis the Martian surface is currently devoid of life turns out to be true or not, scientists will still take extraordinary precautions to ensure their hard-earned samples do not become contaminated with terrestrial microbes and biomolecules. That means maintaining and examining all Mars rock and dirt samples only under the most stringent conditions of biocontainment.

For the sake of scientific investigation, researchers dispatching probes to Mars have worked systematically to avoid accidental forward contamination with stowaway terrestrial microbes (3). Discovering experiments on Mars have been confounded by the presence of terrestrial microbes would be dismaying, but accidental back contamination of the Earth with an unknown form of microbial life might turn out to be utterly disastrous. Well aware of severe and irrevocable outcomes following introductions of invasive species and microorganisms, it is clear the potential consequences of mishap for our biosphere could be profound (1). Under the circumstances, the onus is squarely on NASA to create failsafe methods to preserve and contain Mars samples brought to Earth for analyses. Reflecting the complexity of its many component subprojects, the long timeframe of execution and poorly understood risks with potentially extraordinary geographic range, a Programmatic Environmental Impact Statement (PEIS) must be part of the analysis and approval process. It will be one of the most momentous documents of its type in history.

Everyone Will Want Some of This Action

Competition to examine samples from Mars will probably be intense. Every investigator allowed into this sanctum sanctorum will secure a place in history and legitimate claim to coveted scientific discovery priority. It is possible investigations of Mars samples will be confined to a single purpose-built federal facility. However, because funds always seem limited, arguments to avoid duplication of specialized equipment make it almost inevitable samples will be parceled out to numerous laboratories and investigators. 

Any facilities designated to receive Mars samples will be top flight and overseen by well qualified professionals, so are we safe to assume chances for any mishaps are low? Unfortunately, prior history reveals microbiology laboratory escapes and incidents have been reported frequently enough to be worrisome (4-6). After 9/11, the proliferation of high containment research facilities was identified specifically as increasing the public health risk (7). Although a great number of scientists may hope to work with Mars samples, limiting their distribution will be an essential risk reduction action. It is unclear if maintaining such limits will be politically feasible. 

Did This Train Already Depart the Station? 

NASA planners are a long way down the pike on this one. Anticipating a follow-on mission to transport materials to Earth, the Mars Perseverance rover is collecting and caching samples in Jezero Crater. On one hand, while building on success is good, significant resources have already been expended which increases pressure to push this project forward. On the other hand, perhaps the timing and prior project history will inadvertently constrain the freedom of planners. Required to locate and secure the previously acquired samples, will engineers be compelled to shoehorn them aboard the future transport vehicle employing ‘best-we-can-do’ trade-offs regarding containment and biosafety issues? Cached containers will be exposed to the harsh and dusty conditions of the Martian surface a minimum of several years before collection. Extraordinary actions will be required simply to secure them free of the dust (8) that is so ubiquitous on Mars. More worrisome is the fact that experience shows it is hard to sterilize spacecraft (3) or samples from complex environments like soils.        

Appreciating the Full Scope of This Problem

Administrators of scientific programs often rely on a peer review process to evaluate merits and reveal shortcomings of research funding proposals. Involving experts and capable of prioritizing funding requests according to technical merit and scientific significance, these protocols have served the research community well. Scientific investigation will be at the heart of the Mars sample program, but because the environmental ramifications of this work are potentially so far reaching, the evaluation process will extend far beyond the scientific peer review committee level.  Reflecting the gravity and complexity of the impending determinations, NASA has been designated lead agency for the Mars Sample Return Campaign, although it is not clear precisely where final decision-making authority rests. Plans should be forthcoming in the Programmatic Environmental Impact Statement (PEIS) detailing how cooperating federal agencies with jurisdiction and essential supporting organizations will participate in the Mars Sample Return Campaign.  

Will the scientific community broadly support the effort to transport samples from Mars to the Earth for analysis? We can only wait and see if safety concerns overwhelm an ordinarily predictable enthusiasm to foster scientific achievement. The contentious situation surrounding some “gain-of-function” research may offer an instructive example for NASA. Involving potentially pandemic producing viruses such as influenza, some gain-of-function programs have been criticized as too risky to pursue by peers fearing possible tragic mishaps (9). Should an analogous sentiment that transporting rocks and dirt samples from Mars to Earth is unwise given the current uncertainty about what, if any, viable life forms may be harbored within them take hold within the scientific community, normal peer review evaluations of Mars sample work proposals could be stymied. Worse, in the absence of substantial scientific community consensus, decisions to approve proposed work plans handed down by peer review panels may be attacked after the fact as biased, actions virtually guaranteed to sow confusion and fear in the general public.

The National Science Advisory Board for Biosecurity (NSABB) has been tapped to evaluate certain research programs supported by the National Institutes of Health (NIH) deemed to pose high risks (10). NASA will be well advised to pay heed to the scientific and political issues that ultimately forced this unusual action. Creating an unquestionably independent and unbiased oversight board may be the most challenging and essential task ahead to ensure continued public confidence in the Mars sample return mission.   

When Will the Mars Sample Return Campaign End?

The Mars sample return mission will necessarily unfold over a period of years. While the mission currently being planned has a defined end point, the desire to analyze Mars samples on Earth seems unlikely to be satisfied with a ‘one and done’ effort. As mechanical devices and possibly human beings continue exploring the red planet, more materials, perhaps in greater quantities, will probably be sent back to Earth. Undoubtedly scientists will be eager to investigate the Special Regions (3) and any accessible sites harboring water. Does an active biosphere still exist near or within frozen subsurface waters or other hospitable refuges on Mars? The first trove of small samples collected on the Martian surface may have little potential to harbor viable microbes, but the situations and attendant risks could be vastly different in other locations. Moving forward, it may be wise to require updated risk assessments reflecting the specific level of biocontamination risk prior to approving future Mars sample return missions.

Now or Never? 

NASA has published a Federal Register notice stating a draft PEIS will be available for public inspection in the Fall of 2022 with the Record of Decision anticipated to follow in Spring/Summer 2023 (11). Involving as it does flight hardware and processes in final design phases, coordinating input from multiple cooperating federal agencies along with perhaps other contractors/organizations with special expertise while addressing public comments received during the recently concluded project scoping phase, this timeline would be extremely optimistic even for a routine project. Factor in potentially incalculable environmental risks, an urgent need to devise impartial research conduct oversight mechanisms, complicated biosafety considerations combined with an existing base of opponents present within the scientific community itself (2) and it is clear this task will be as complex as the flights and sample recovery operations to be executed on Mars. Hopefully, the sample containers cached by the Perseverance rover are durable because they may be stuck on the red planet for a long time.    

The extraordinary scientific significance of this project and its many ramifications guarantee intense interest and scrutiny. This Programmatic Environmental Impact Statement creation process is open to the public (11) making it imperative the planning to preserve and contain the returned Martian samples safely be as proactive, thorough and every bit as attentive to detail as the work performed supporting the flight phases of this transport mission. Anything less and NASA may discover its premier program has been grounded. 

 (1) Nell Greenfieldboyce. NASA is Bringing Rocks Back from Mars, but What if Those Samples Contain Alien Life? NPR, 4 May 2022. https://www.npr.org/2022/05/04/1095645081/nasa-is-bringing-rocks-back-from-mars-but-what-if-those-samples-contain-alien-li   

(2) International Committee Against Mars Sample Return. https://www.icamsr.org/index.html

(3) Alberto G. Fairén.  2017. 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

(4) Martin Furmanski. 2014. Threatened Pandemics and Laboratory Escapes: Self-Fulfilling Prophecies. Bulletin of the Atomic Scientists, 31 March 2014.  https://thebulletin.org/2014/03/threatened-pandemics-and-laboratory-escapes-self-fulfilling-prophecies/

(5) Jocelyn Kaiser. 2014. Lab Incidents Lead to Safety Crackdown at CDC. Science, 11 July 2014. https://www.science.org/content/article/lab-incidents-lead-safety-crackdown-cdc

(6) Kelsey Piper. 2019. How Deadly Pathogens Have Escaped the Lab – Over and Over Again. Vox, 20 March 2019.  https://www.vox.com/future-perfect/2019/3/20/18260669/deadly-pathogens-escape-lab-smallpox-bird-flu

(7) Jocelyn Kaiser. 2007. Proliferation of Biosafety Labs Poses Its Own Risks, Congress Told. Science, 4 October 2007. https://www.sciencemag.org/news/2007/10/proliferation-biosafety-labs-poses-its-own-risks-congress-told

(8) Mary Kekatos. 2022. Mars Lander Losing Power Because of Dust on Solar Panels. ABC News, 18 May 2022. https://abcnews.go.com/Technology/mars-lander-losing-power-dust-solar-panels/story?id=84805112

(9) Carl Zimmer and James Gorman. 2021. Fight Over Covid’s Origins Renews Debate on Risks of Lab Work. The New York Times, 20 June 2021. https://www.nytimes.com/2021/06/20/science/covid-lab-leak-wuhan.html

(10) Joel Achenbach. 2022. NIH Orders Sweeping Review of Potentially Risky Experiments on Viruses and Other Pathogens. The Washington Post, 1 March 2022. https://www.washingtonpost.com/health/2022/03/01/nih-review-lab-safety/

(11) Mars Sample Return Campaign PEIS https://www.govinfo.gov/content/pkg/FR-2022-04-15/pdf/2022-08088.pdf

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The World is My Oyster Pandemic

SARS-CoV-2 and its variant offspring are running rings around the world. As the Omicron variant fades, can authorities finally eliminate all pandemic restrictions mandated on a weary public? The short answer on eliminating masks and other measures is yes, but the real question is whether the threat has declined sufficiently to warrant that action. At the moment it is hard to be sure where we are in the complex and unpredictable ebb and flow of this disease. Maybe the combined effects of vaccination and fresh herd immunity will protect most of us in the near future. On the other hand, after anticipating being done with COVID last July, we have experienced the swift rise of several variant viruses. If Omicron or its sub-variant BA.2 have a virulent successor, will the public accept a return to restrictions after they have been lifted? Unfortunately, the authorities may be forced to address that question soon.            

Cover the Earth

As long as people get infected with coronavirus, we face a persistent risk new variant strains will emerge somewhere. Prior experience reveals that no matter where they happen to appear, some of these new virus forms are capable of marching over the entire world with stunning speed.

The dire situation may become increasingly challenging because virus transmission is encompassing more than human populations. Armed with a capacity to infect a broad range of species, the human pandemic has set the stage for susceptible wild animals such as deer (1, 2) to become fertile new grounds for SARS-CoV-2 invasion. 

The ultimate ramifications of this explosive expansion in SARS-CoV-2 range for infectious disease and planetary ecology are unpredictable. For example, if the viruses currently circulating in humans evolve toward more benign forms (3), i.e., become endemic as some people describe it, could we relax only to see existing reservoir species or newfound hosts like deer brew up unique coronaviruses (3) that turn out to be deadly to humans? A global experiment is underway.

Can We Avoid More Disasters?

Knowing wild animals exploited as food sources indisputably have been infection sources for several viruses (4) should prompt more changes in how we manage them. Despite efforts to clarify its genesis, the exact sequence of events that sparked the COVID-19 pandemic remain uncertain and controversial; did SARS-CoV-2 leap into humans out of a wet market, a natural setting or a laboratory? Did the Omicron variant evolve in an immunosuppressed human being or through some other mechanism? In principle, an accurate understanding as to how the current pandemic got started and evolved might help us avoid repeating catastrophe. Unfortunately, we have to wonder and worry whether the expanding list of natural reservoir species, new opportunities for transmission (1-5) and burgeoning geographic range of this particular virus increases the risk of future deadly pandemics. The world is changing before our eyes. 

As much as we may wish the decline in Omicron cases signals an end to the pandemic and return to normalcy, the situation is complicated and becoming more complex. Maybe evolution will hone SARS-CoV-2 into something akin to the currently known human coronaviruses that generally produce mild disease (3). Still, an adaptable beast is on the loose within us and perhaps this means we are fated to experience wave after wave of nasty, world-traversing variants (3). However, the coronavirus pandemic has been consistently unpredictable, so maybe better days do lay just ahead. While we wait for SARS-CoV-2 to evolve, we have the luxury of choosing which hypothesis to believe.              

For SARS-CoV-2 and other potentially pandemic-producing viruses, the whole world is wide open. We, hopefully, will devise ways to live within this harsh new reality. 

(1) Vanessa L. Hale et al. 2021. SARS-CoV-2 Infections in Free-Ranging White-Tailed Deer. Nature, 23 December 2021. https://www.nature.com/articles/s41586-021-04353-x

(2) Emily Anthes and Sabrina Imbler. 2022. Is The Coronavirus in Your Backyard? The New York Times, 7 February 2022. https://www.nytimes.com/2022/02/07/health/coronavirus-deer-animals.html  

(3) Donald S. Burke. 2022. Coronaviruses are “Clever”: Evolutionary Scenarios for the Future of SARS-CoV-2. Stat, 16 February 2022. https://www.statnews.com/2022/02/16/coronaviruses-are-clever-evolutionary-scenarios-for-the-future-of-sars-cov-2/

(4) Jon Cohen. 2022. Wild Animals Prized as Delicacies in China Contain a Bevy of Threatening Viruses.  Science, 17 February 2022.  https://www.science.org/content/article/wild-animals-prized-delicacies-china-contain-bevy-threatening-viruses

(5) Emily Anthes. 2022. In New York City Sewage, a Mysterious Coronavirus Signal. The New York Times, 3 February 2022. https://www.nytimes.com/2022/02/03/health/coronavirus-wastewater-new-york.html?smid=tw-share  

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Update

Sabrina Imbler and Emily Anthes. 2022. The Coronavirus Menagerie. The New York Times, 22 February 2022. https://www.nytimes.com/2022/02/22/health/coronavirus-animals.html

Is Proxima b A Party Planet?

Dr. Avi Loeb is an accomplished scientist, but a recent opinion piece published in The Hill (1) reminds us his bold, public expressions of some unconventional views make him an outlier in his professional community. I do not know how many scientists believe that interstellar object ‘Oumuamua is a device constructed by intelligent aliens or that federal funding support for programs to scan planet Proxima b for city lights is warranted. However, a quick survey of the news media and other information sources will reveal how many of them are active champions of such notions.

Few ideas captivate the public imagination like the prospect of encountering intelligent life in the Cosmos. Dr. Loeb also heads The Galileo Project (2) “to bring the search for extraterrestrial technological signatures of Extraterrestrial Technological Civilizations (ETCs) from accidental or anecdotal observations and legends into the mainstream of transparent, validated and systematic scientific research,” making it fair to assert he has captured the particular attention of what might loosely be termed the UFO community. To what end? 

Danger, Will Robinson!

Dr. Loeb appears to have deliberately embarked on a career high wire act and I wish him the best of luck in this complicated undertaking. Is it possible for elements of a raucous UFO community to find productive common cause with mainstream scientists in a systematic and rigorous search for evidence of intelligent extraterrestrial life? Time will reveal if we are witnessing a courageous visionary on the cusp of multiple momentous discoveries, whether enthusiasm sparked by new observations got the better of seasoned professional judgement or some of both are in play. 

Notwithstanding a shared interest in exploring the unknown, scientists can be brutal in their assessments of unconventional ideas deemed unsupported by objective facts. Using one of the unquestionably finest telescopes of his era, Percival Lowell gathered a body of primarily visual observations he deduced revealed a civilization struggling to survive on a drying planet Mars (3). A successful businessman boasting spectacular achievements at the cutting edge of Astronomy, Mr. Lowell was well known to the general public and a short review of his book, Mars as the Abode of Life, was published in the prestigious journal Science (4). The reviewer noted that although Mr. Lowell had not produced an outright fantasy, he had so blurred essential distinctions between personal opinions and facts that the book warranted being judged misleading pseudoscience.

Reading Dr. Loeb’s opinion piece positing city lights, continents, frequent birthday celebrations and possible imputations regarding the global technology/politics/customs extant on planet Proxima b reminded me how Percival Lowell blazed his lonely trail by founding a private observatory and building his own telescopes. New instruments will be doubtlessly constructed for astronomers, but the rationale as put forth by Dr. Loeb in his opinion piece alone seems unlikely to persuade skeptical scientific peer reviewers or impel funding agencies to act in the event forthcoming tools like the James Webb Telescope fail to capture clear evidence of artificial lights or huge solar panel installations on Proxima b. The idea scientists armed with a powerful telescope could detect an alien civilization by observing the frequent birthday celebrations on the dark side of a hypothetically inhabited nearby planet rests not on a body of objective evidence, but a gossamer thread of contrived high hopes. Will a high-risk, high-reward research hypothesis based on such a factually wispy rationale be rated favorably enough by peers to be allocated observing time on the Webb Telescope or any other instruments?    

With ‘Oumuamua too distant for additional study, no one knowing when the next interstellar object might zip past Earth, intense competition for instrument observing time and a new super telescope still years away, Dr. Loeb may have a long wait for any of his more unconventional ideas to be confirmed through direct observation. The Galileo Project could conceivably fill that gap by discovering something spectacular. However, if I were Dr. Loeb, I would be worried this tricky effort will not yield anything of note quickly and leave me with evaporating public support and irritated professional peers. With so much at stake, let’s hope he has a viable career plan B.  

Abandoning the Art of Leaving Out 

Scientists extrapolate their findings and speculate about their ramifications in journal articles and formulate testable hypotheses to frame research funding proposals. However, the art in this part of the job is recognizing the community norms constraining these activities. In other words, it is important to have a feeling for what peer reviewers will deem acceptable deductions and reasonable interpretive license based on the data in hand. You also learn that no matter how elegant they may be or how dearly you love them, some insights and experiences do not fall within the constrained interest scope of professional publications. 

In his book, The Unexpected Universe (5), Anthropologist and naturalist Loren Eiseley summed up a personally transcendent experience involving a fox kit this way; 

“It is the gravest, most meaningful act I shall ever accomplish, but, as Thoreau once remarked of some peculiar errand of his own, there is no use reporting it to the Royal Society.”

Dr. Eiseley demonstrated there are places to publish such accounts and Dr. Loeb may likewise be actively seeking out a broader audience and the unique opportunities that could come with it. Perhaps a billionaire inspired by reading Dr. Loeb’s evocative writings will provide the financial support necessary to reveal if Proxima b is a party planet. However, it seems a safe bet no awards will be forthcoming until after the full confirmatory light curve data is published in the peer-reviewed scientific literature. 

(1) Avi Loeb. 2022. Why NASA Should Build an Even Bigger Telescope. The Hill, 3 February 2022. https://thehill.com/opinion/technology/592719-why-nasa-should-build-an-even-bigger-telescope

(2) The Galileo Project. https://projects.iq.harvard.edu/galileo/home  

(3) Percival Lowell.  1908.  Mars as the Abode of Life.  Reprinted (2000) by Bohn Press.

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

(5) Loren Eiseley. 1969. The Unexpected Universe. Harcourt Brace Jovanovich, New York. (p. 212)

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A UFO Renaissance?

A few days ago, a friend revealed he had encountered a large, black object maneuvering silently in the night sky. It vanished, leaving him wondering what he had seen.

I suggested his experience is a classic UFO sighting report in many ways and went on about how Arizona seems to be a hot spot for such things. Living as he does near several active defense installations and testing/training reservations, sightings of military aircraft are frequent. However, what my friend witnessed was unlike anything familiar to him. I suspect that although he recognizes he may have accidentally observed a flight of a top secret military aircraft, the sighting and its possible ramifications shook him.

Now What?

Newly drafted into the realm of UFO experiencers, I have to wonder what the aftermath of this event will be for my friend. He confided in me because he knew of my longstanding interest in UFOs, but I felt compelled to advise him that repeating his account may incite more jokes and ridicule than serious consideration. I hope I was able to convey the message that he is not alone.     

He may have assumed I would know where reliable information on the subject could be found. He didn’t reveal whether he had searched out more information on the topic, but since he does follow mainstream news reports he probably has seen some of the recent surge of stories about UAP (unidentified aerial phenomena) sightings involving the U.S. military (1) and the free-for-all these reports have ignited (2). However, little in the latest UAP news speaks to his personal experience directly. 

A great deal of information has been posted on blogs and I recommended my friend start his journey by having a look at Jack Brewer’s blog, The UFO Trail (3), and listen to a re-launch of the Paratopia Podcast produced by the late Jeff Ritzmann and Jeremy Vaeni (4). 

The history of the UFO phenomenon in the U.S. has a dark side and to orient a newcomer to ‘men-in-black’ intrigues and other issues I recommended reading Adam Gorightly’s recently published book Saucers, Spooks and Kooks (5) and viewing the documentary Mirage Men (available on Amazon Prime). One investigator has compiled a list of scholarly works on UFOs and allied topics on his Ufology Research blog (6). (h/t to Sarah Scoles, author of They are Already Here, for pointing out this resource in her Twitter feed.)

Change is Coming

Scientific community interest in UFOs has fluctuated widely over the years. Notwithstanding the well-worn refrains that scientists ignore or are afraid of the topic, a search of the prestigious journal Science, published by the American Association for the Advancement of Science, reveals a substantial number of articles, news reports, letters and book reviews on UFO/flying saucers were featured over the years. While scientist evaluations of specific UFO studies and evidence have often been scathing, the body of work published in Science has not been uniformly dismissive of the topic (7). Spurred by observations of the first confirmed interstellar object and concurrent reports of UAP events recorded by military personnel, a new scientific research initiative, The Galileo Project (8), has been launched. Perhaps humankind is on the verge of a new comprehension of the Universe and our place in it. 

This may be a good moment in time to be drawn into the UFO mystery as change seems to be on the way for the scientific backwater of UFO research. For decades work has been conducted by solitary, part-time investigators of variable levels of competence. Is the center of productive investigation poised to become the presumably adequately-funded and well-equipped Department of Defense UAP investigation program? How much of what the military discovers will be classified and unavailable to the general public? Are we in for breath-taking disclosures or a high-tech re-play of Project Blue Book? Maybe The Galileo Project is the best hope for the fullest possible public release of facts and discoverable evidence underlying the UFO phenomena. We must wait for whatever findings the new gatekeepers decide they are willing to present.

Fair warning to any intrepid souls seeking to plumb the depths of the UFO subculture; you will encounter situations that unleash powerful emotions. Joy, awe and fear may find you, but also be prepared for seething rage when you recognize how some callous and malignant charlatans have found a means to perpetrate unspeakable outrages against our fellow human beings.        

UFO study is a challenging endeavor and I do not claim to know what the coming research efforts will yield. However, I will predict that anyone undertaking a quest to comprehend the UFO mystery will ultimately realize many facets of the human experience are reflected in it clearly.

(1) Bill Chappell. 2021. How UFO Sightings Went from Conspiracy Theory to a Serious Government Inquiry. NPR, 4 June 2021. https://www.npr.org/2021/06/04/1003262749/how-ufo-sightings-went-from-conspiracy-theory-to-a-serious-government-inquiry  

(2) Alex Seitz-Wald. 2022. Disclosure or Deception? New UFO Pentagon Office Divides Believers. NBC News, 8 January 2022. https://www.nbcnews.com/politics/national-security/disclosure-or-deception-new-ufo-pentagon-office-divides-believers-n1287199

(3) Jack Brewer. The UFO Trail.  http://ufotrail.blogspot.com/

(4) Jeff Ritzmann and Jeremy Vaeni. Paratopia. http://paratopia.net

(5) Adam Gorightly. Saucers, Spooks and Kooks. UFO Disinformation in the Age of Aquarius. Daily Grail Publishing, Brisbane, Australia, 2021.

(6) Ufology Research Blog. https://uforum.blogspot.com/2022/01/scientific-and-scholarly-articles-about.html

(7) David Kestenbaum. 1998. Panel Says Some UFO Reports Worthy of Study. Science, 3 July 1998. https://www.science.org/doi/10.1126/science.281.5373.21a

(8) The Galileo Project. https://projects.iq.harvard.edu/galileo/home

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Nature, Nurture, Culture and Biotechnology Start-up Companies

 An editorial by the editor-in-chief of Science journals described the interplay between the culture of science and a visionary entrepreneur (1). A heavy focus on charisma coupled with a certain amount of fakery being considered acceptable in this arena (1) ultimately yielded a truly devastating outcome for Elizabeth Holmes, the investors in the company she launched, Theranos, and its employees. 

As this sad story grinds through to a disgraceful end in the legal system, can anything be learned to prevent such debacles in the future? Is this situation a simple one-off crime or have deep underlying problems in how promising scientific advances are converted into remarkable private sector enterprises been exposed?

A Culture of Hype? 

As much as we might prefer to identify a villain to blame, several factors contributed to the cursed birth and death of Theranos. Igniting enthusiasm is a component of successful research grant awards. However, achieving that with an audience of true peers is one thing, trying to capture the attention of potential investors is probably a different endeavor. I am not accusing anyone of telling lies, but can appreciate how under some circumstances raw enthusiasm might spontaneously grab the reins and run with a presentation beyond the advisable limits of established facts.  

If there is a pervasive culture of hype in science, it is not clear Elizabeth Holmes had much time to internalize it since she was so young at the outset of her Theranos project. This was not someone who spent years writing grant proposals while absorbing the norms of the biotech community, although she did seem to consciously emulate Steve Jobs in some ways. However, it is possible that the group of capable scientists and technical advisors she attracted coached her in the fine art of high-tech research and development hype. Perhaps that hypothesis will be clarified in the legal proceedings still to come.   

Back to the Basics?

Could an overboard hype problem be controlled by relying on accomplished scientists armed with data-rich – and probably boring – PowerPoint presentations? The first rule of communication is to know your audience and I will hazard a guess that approach, although pleasing to many academics, will not be competitive in the cut throat real world of start-up companies.

Working as a scientific consultant for a biotech company, I met someone who told me a fascinating story about a past investment opportunity. He and a few co-workers at a large communications company had been seeking out small start-ups hoping to attract funding. Two guys gave them a presentation, but the group declined to invest, feeling they were inexperienced and did not inspire confidence they would succeed. Only later did it become clear they passed on what might well have been a life-changing investment. 

Impressions and appearances will inevitably influence our decisions. My suggestion for prospective investors facing inspirational presentations delivered by ‘force-of-nature’ entrepreneurs is to always seek a second, informed opinion. Find a faculty member consultant with experience in the area or hire a graduate student to comb through the prospectus and set the claims in true factual context for you. Called on to perform peer reviews of funding proposals and publications, scientists are skilled at deconstructing data interpretations and arguments. You just need to find the ones without competing interests in the work or distracted by a well-polished funding pitch. Or a lack luster one.                           

(1) H. Holden Thorpe. 2022. When Hyping Technology is a Crime. Science, 13 January 2022. https://www.science.org/doi/10.1126/science.abo0022

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With a Little Help From Our Friends – A Heart Xenotransplant

The first living human patient has received a heart transplant from a genetically modified pig (1). Does this herald a time when wait lists for organ transplants become a thing of the past? Could patients suffering with kidney failure avoid long duration dialysis treatment? This bold effort inspires hope, but there is no telling how far we have to go before such dreams are realized.     

As is often the case, a convergence of factors enabled this medical milestone to be reached earlier than many anticipated (2). However, although human-to-human heart transplants have been performed for decades, this particular effort is a complex set of experiments and the ultimate outcome is in doubt. The transplanted organ is not exactly a pig heart; it has been genetically modified to dampen rejection and augmented with some human genes to help it function better in its new host. Experiments in animals provide a basis for optimism (3), but no one could know how well and how long this heart transplant strategy would succeed in a human patient until it was actually implemented.

Wishing the best for this patient and those to come, the genetic engineers, surgeons and scientists must stand and wait for the processes to unfold and hope they have anticipated the foreseeable pitfalls correctly.  

It is possible the next steps toward transhumanism will only be possible with help from our animal friends. If so, the intrepid medical transcendentalists of the future will be demonstrably more than human.

(1) Roni Caryn Rabin. 2022. In a First, Man Receives a Heart from a Genetically Altered Pig. The New York Times, 10 January 2022.  https://www.nytimes.com/2022/01/10/health/heart-transplant-pig-bennett.html

(2) Elie Dolgin. 2021. Skin, Nerve Transplants from Genetically Modified Pigs Could Help Humans, but Organs Are a Way Off. Science, 1 November 2021. https://www.science.org/content/article/skin-nerve-transplants-genetically-modified-pigs-could-help-humans-organs-are-way

(3) Kelly Servick. 2017. Scientists Grow Bullish on Pig-to-Human Transplants. Science, 22 September 2017. https://www.science.org/content/article/scientists-grow-bullish-pig-human-transplants

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Big Science Takes the Stage

A company aptly named Colossal (https://colossal.com/company/ ) has announced an effort to recover the woolly mammoth from extinction (1). The ultimate goal of this daunting project is to produce thousands of mammoth genetic facsimiles and re-wild herds of them in the arctic tundra. The great hope is replacing this long lost keystone species with functional analogues would help limit carbon releases into the atmosphere and thereby mitigate global warming. Achieving these objectives will pose immense technical as well as political and ethical challenges (1, 2).

Desperate Times Ahead

Environmental changes due to human activities have produced some unanticipated adverse consequences for our health and wellbeing. As journalist Elizabeth Kolbert points out in her book, Under a White Sky (3), we are entering a time in which human engineering of nature will become more complicated, far-reaching in scope and urgent. Compared to some geoengineering proposals, the woolly mammoth de-extinction project seems positively benign.  

If there is a general problem with schemes to mitigate global warming or other geoengineering issues it is that environments are complex and hard scientific knowledge about their dynamics is rudimentary. Consequently, proposals to do things like block solar radiation by injecting reflective aerosols into the stratosphere seem eminently logical, but intrinsically risky since the downstream and long-term impacts on the affected regions are uncertain. Calls to increase research funding have been issued (4) and we will have to wait to see if public anxiety over the impacts of climate change increase to a point at which demands for action be taken regardless of ethics or risk. At the moment the world seems to think all that we need to do is decrease fossil fuel carbon emissions.

No Competing Interests?

We are already seeing some scientific research transition from controlled laboratory endeavors to environmental engineering-scale experiments. Working to resurrect woolly mammoth analogues and re-wild great herds of them in the arctic, Colossal hopes to discover bioengineering and intellectual property profit centers along the way (1, 2). Although teamed with academic researchers and focused on goals that will further the general public interest such as helping to mitigate global climate change, Colossal is a clearly commercial enterprise. However, this is truly new territory and the situations are not always as clear cut. Academic researchers have proposed a new environmental modification approach to control Lyme disease (5) and are seeking public support to translate laboratory research into practical solutions to a troubling real world public health problem. To be clear, controlling Lyme disease by genetic modification of a living ecosystem is not a known solution to Lyme disease any more than setting loose mammoth hybrids in the tundra is the answer to climate change. The Lyme disease researchers are simply further along and building support to run their experiment on the environment. 

Whether commercial, academic or something in between, the common thread between the diverse groups and the array of problems they are addressing appears to be a sincere desire to help improve human and environmental health. However, whether driven by the profit motive or able to honestly declare they have no competing interests, it seems likely all of them would also love to be able to seize the acclaim that would come with success. No matter how such situations are defined and declared in academic publications, wanting the glory of solving the problem can be a competing interest as potent as any financial gain.

Researchers are about to embark on high-stakes translational environmental research and development/deployment programs; efforts that will test our sense of ethics and capacity to assess risks as never before. All the world’s a stage and audience participation will be mandatory. 

                       

(1) Carl Zimmer. 2021. A New Company with a Wild Mission: Bring Back the Woolly Mammoth. The New York Times, 13 September 2021. https://www.nytimes.com/2021/09/13/science/colossal-woolly-mammoth-DNA.html?smtyp=cur&smid=tw-nytimesscience

(2) Victoria Herridge. 2021. Before Making a Mammoth, Ask the Public. Nature, 20 October 2021. https://www.nature.com/articles/d41586-021-02844-

(3) Elizabeth Kolbert. 2021. Under a White Sky: The Nature of the Future. Crown, New York

(4) Warren Cornwall. 2021. Panel Calls for $2.5 Billion in Ocean Geoengineering Research. Science, 8 December 2021. https://www.science.org/content/article/panel-calls-2-5-billion-ocean-geoengineering-research

(5) Joanna Buchthal et al. 2019. Mice Against Ticks: An Experimental Community-Guided Effort to Prevent Tick-Borne Disease by Altering the Shared Environment. Philosophical Transactions of the Royal Society B 374: 20180105 https://doi.org/10.1098/rstb.2018.0105

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The Instrumentality of Life – Will Synthetic Mammoths Miss Their Mothers?

Is anyone in charge of resurrecting woolly mammoths? A visionary private company is seeking to mass produce genetic hybrid facsimiles of the extinct beasts in the hope herds of them in the tundra could help stave off global warming (1), so a few questions now seem to be in order. Victoria Herridge considers the ethics of undertaking such an enormously far-reaching effort in an essay published in Nature (2). Her solution; proactively seeking explicit public approval to proceed, is revolutionary, but not entirely unprecedented.

Halting a cutting-edge research effort that is itself a hybrid of aligned private and academic assets may not be possible and Dr. Herridge is not promoting such drastic action. Some safeguards are in place to ensure the proper care and use of experimental animals and this work will almost certainly go forward to some extent. However, the usual and customary animal care assurances may not quite cover what looms in our fast-approaching future. If all goes according to the current plan, motherless elephant-mammoth hybrids, the synthetic biology analogues of Dr. Frankenstein’s creature, will emerge from the laboratory. 

An Audacious, if Indirect, Path to the Future 

Whether assembling genetic patchwork creatures and letting colossal herds of them loose to test vague notions about mitigating global warming gives anyone pause or provokes public backlash remains to be seen. Notwithstanding the logic behind deploying herds of woolly mammoth analogues to stomp out tundra moss and thereby help manage global climate change, that idea seems more like a proactive public relations ploy than geo-engineering research plan. Scientists are on a path that may lead to some disquieting activities, but at least they can point to an overarching beneficial rationale for their work. The good news is that a group that cares about public opinion may be amenable to the sort of open approach that Dr. Herridge advocates. 

The work is groundbreaking, but the initial phases at least will not be classic hypothesis-driven research and ordinary academic output (1); this will be new generation genetic manipulation tools and techniques development. The ultimate implications of this effort will be unimaginably far reaching as others capitalize on a builder’s bonanza and harness these powerful instruments to bring their own personal visions into being. 

The de-extinction of the woolly mammoth was enticing enough to attract private funding (1) for work that may be too far out for federal granting agencies. Nonetheless, that situation makes a number of useful things possible in a short timeframe and perhaps with less bureaucracy. It will be interesting to see how far the goal of de-extinction is pursued as bench work proceeds, workers acquire experience-based perspectives on technical feasibility and new, possibly more enticing, opportunities arise. 

Creating the First Genetic Orphans? 

If the technical issues ahead of creating cold-tolerant elephant-mammoth hybrids are formidable, the ethical considerations are mind-boggling steps beyond (1, 2). These evolutionary orphan creatures from artificial wombs will have no mothers and no elders; how will they behave, be socialized into herds and cared for in the years it will take for them to mature? 

In one sense, maybe the research will come to the rescue. As this group of intrepid scientists develops new tools to manipulate formerly impossibly large DNA molecules, they might get so good at it that replacing elephant genomes with enormous swaths of reconstituted mammoth nucleic acids or whole chromosomes becomes feasible. The future iterations of these resurrected creatures might be, genetically at least, a great deal more woolly mammoth than elephant. Scientific research is an enterprise that builds on its achievements, so it seems reasonable to project investigators will be expanding their own powers to create on a continuous basis. From a purely scientific standpoint all to the good. However, if new and improved genetic models supersede the old, we could have a novel situation where generations of imperfect or outmoded hybrids exist. What will become of our creations who have no mothers to watch over and weep for them? 

                                

(1) Carl Zimmer. 2021. A New Company with a Wild Mission: Bring Back the Woolly Mammoth. The New York Times, 13 September 2021. https://www.nytimes.com/2021/09/13/science/colossal-woolly-mammoth-DNA.html?smtyp=cur&smid=tw-nytimesscience

(2) Victoria Herridge. 2021. Before Making a Mammoth, Ask the Public. Nature, 20 October 2021. https://www.nature.com/articles/d41586-021-02844-5

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The Silence of the Scientists

Did the COVID-19 pandemic originate through a sequence of natural events or was it touched off by a laboratory leak? With millions dead and possibly millions more yet to die, pinning down a fact-based consensus view as to how this disaster started has become an exercise in futility. Each day seems to bring more concerns and notwithstanding an official WHO investigation, worrying questions remain unresolved (1).

Nightmares for Gain-of-Function Researchers

The inability to settle questions concerning the origin of the COVID-19 pandemic does seem to have spawned some consequences. Legislation (Bill HR 5270) mandating a 5-year suspension of funding for gain-of-function research conducted on certain viruses has been introduced to the U.S. Congress and referred to committee (2). The “Pausing Enhanced Pandemic Pathogen Research Act” is intended to prevent U.S. taxpayer funds from falling into what is loosely termed the “wrong” hands, in this specific instance, groups laboring to make certain influenza and coronaviruses more pathogenic. The ultimate legislative fallout over the battle to pin down the origins of the COVID-19 pandemic, this bill apparently has bipartisan support.

The prospect persons outside the small circle of specialists who have been setting regulations and doling out funds might summarily cease federal support for their programs is a nightmare scenario for gain-of-function researchers. Experiments with influenza and other potentially pandemic producing viruses have generated controversy within the scientific community for over a decade, but the emergence of COVID-19 has focused more attention on this research program area and its striking lack of transparency (3). Troubling revelations seem to bubble up daily while efforts by American and British officials to keep discussions of pandemic origins by scientists confidential (4) fan the flames of conspiracy accusations and corrode the public faith in experts. 

And What About China?   

To rally support for gain-of-function research the ‘if we don’t do it, someone else will’ rationale may be deployed. This maneuver sidesteps discussion as to whether the projected benefits of the work are worth the risks while invoking vague fears of unnamed adversaries and their unknowable intentions. However, in the case of coronavirus research, this argument is more compelling than usual. Chinese scientists were active partners in an international effort to identify and study potentially pandemic coronaviruses suggesting they, or others who read the scientific publications resulting from this collaborative project, could carry the work forward in the event the U.S. Congress cuts off funding. Facing the prospect of continued emergence of dangerous viruses from local zoonotic reservoirs, it seems reasonable Chinese officials would be motivated to pursue programs to identify the threats and devise ways to actively suppress them with or without U.S. support.

Should Chinese scientists be forced to pursue pandemic virus surveillance and mitigation research alone, it seems reasonable to impute they will go about the work with care. However, the political climate in China with regard to pandemic virus research also seems to have undergone a notable shift. Recent news reports reveal Chinese officials intend to keep a careful watch over the laboratories engaged in such studies (5). The timing is interesting, but this declaration does not necessarily indicate Chinese officials believe the COVID-19 pandemic originated in a laboratory. It does suggest leaders have recognized research involving potentially pandemic pathogens demands careful and proactive oversight.      

Speak No Evil, the Secret of Successful Scientists?

Succeeding as a scientist requires some degree of community endorsement and fear of retribution may discourage taking any actions that might alienate peers. Many prominent scientists have taken strong, public stances on gain-of-function research, but as matters stand there is no way to judge whether a general reluctance to speak publicly about contentious matters has impacted the intense debate on this matter. Perhaps researchers prefer to defer policy questions to those with the most technical expertise in the area. A reasonable idea, although it might unwittingly abandon the field to those with the greatest level of vested interests in the work area. Worse, one eminent scientist’s personal experience suggests researchers tend to downplay the risks of their own research areas (6). The dilemmas involved in obtaining candid evaluations of research are well known within the scientific community and work-around strategies such as anonymous peer review are employed to minimize the problem. However, assuring the public receives reliable and unbiased assessments of controversial research programs is a far more challenging and unsolved problem.  

Correspondence published recently in the journal Nature (7) conveys information of extraordinary relevance to the arguments raging over gain-of-function research today. Written decades after fast-emerging events alarmed two then-junior scientists, this telling letter confirms worries over antagonizing senior colleagues dissuaded them from expressing their misgivings. Today’s letter goes on to caution us, “Then, as now, what is the right experiment to do should not be determined by scientists alone.” The voice of experience reminds us a broad perspective is essential and a scientific community subset apparently struggling to speak the full truth both to itself and the general public should not be granted sole authority over gain-of-function research conduct and information pertaining to it.     

  1. Chloe Tenn. 2021. WHO Restarts Investigation of COVID-19 Emergence With New Panel. The Scientist, 28 September 2021. https://www.the-scientist.com/news-opinion/who-restarts-investigation-of-covid-19-emergence-with-new-panel-69244
  2. Kiran Stacey. 2021. Controversial Virus Research Sparks Political Debate in U.S. Financial Times, 26 September 2021. https://www.ft.com/content/b328636c-1149-4562-aa6f-f1b0302d3ab9
  3. Nell GreenfieldBoyce. 2020. How Much Should the Public Be Told About Research Into Risky Viruses? NPR All Things Considered, 21 January 2020. https://www.npr.org/sections/health-shots/2020/01/21/797427523/how-much-should-the-public-be-told-about-risky-virus-research
  4. Ian Birrell. 2021. What Are They Hiding? Daily Mail, 2 October 2021. https://www.dailymail.co.uk/news/article-10052689/Government-condemned-refusing-release-details-key-email-conversations-Covid-origins.html
  5. Eduardo Baptista. 2021. Xi Jinping Warns That Chinese Laboratories Handling Deadly Pathogen Will Face Closer Scrutiny. South China Morning Post, 30 September 2021. https://www.scmp.com/news/china/science/article/3150777/xi-jinping-warns-chinese-laboratories-handling-deadly-pathogens
  6. Paul Berg. 2008. Asilomar 1975: DNA Modification Secured. Nature, 455:290-291. https://www.nature.com/articles/455290a
  7. Matthew Cobb and Robert Pollack. 2021. A Dangerous, Wrong or Unneeded Experiment? Don’t Do It. Nature, 594:496, 24 June 2021. https://www.nature.com/articles/d41586-021-01702-8

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