A crowd-sourced Indiegogo funding campaign that raised over $45,000 for do-it-yourself gene editing kits in December, asks: “If you had access to modern synthetic biology tools, what would you create?”  This campaign, which aims to democratize science “so everyone has access,” was launched by Josiah Zayner, who earned a PhD in Molecular Biophysics from the University of Chicago.  For $130 Zayner offers a DIY CRISPR kit that “includes everything you need to make precision genome edits in bacteria at home including Cas9, gRNA and a Donor DNA template.”  This Indiegogo campaign has a special Note to BioHackers: “Each kit comes with all sequence and cloning detail so you can perform your own custom genome engineering.”

Genetically modified organisms, created with CRISPR or other technologies, have the potential to run wild and cause harm to human health and ecological communities.  Zayner’s Indiegogo campaign attracted supporters from around the world, including many nations where there are no clear laws about containment for organisms that have been “biohacked.”  The Federal Bureau of Investigation has targeted hacking communities with the Bioterrorism Protection Team to ferret out possible malicious uses of emergent technologies.  Biohacking can pose significant risks, according to Charis Thompson, Professor of Sociology at University College London and at UC Berkeley.  But security concerns should not blind us to the creative potentials of tools like CRISPR, she says.  During Thompson’s recent address to the Human Gene Editing Summit in Washington she asked: “Are the biosecurity risks exaggerated for citizen use of these technologies? What are the creative and democratic potentials of these techniques?”

Biological artists, or bioartists, have been exploring the creative potential of molecular tools for over fifteen years.  Early examples of bioart illustrate how artists and hackers might use emergent gene editing tools like CRISPR in the near future.  When Eduardo Kac partnered with French biologists in February 2000 to produce GFP Bunny, a living transgenic animal with the green fluorescing protein, some critics dismissed it as a frivolous use of biotechnology.  For others, this artwork presented an opportunity to address ethical issues about life forms that have been created by science and are now dependent on human care for their survival. “Responsibility is key,” Kac insisted. Transgenic art must be accompanied by “a commitment to respect, nurture and love the life thus created,” he said.[i]

Hobbyists who tinker with gene editing tools usually have scarce resources and limited capacity to create potentially harmful organisms, when compared with university, government, and corporate laboratories.  As of August 2015, four biotech startup companies focusing on health applications of the technology have raised at least $158-million in venture capital.  Vertex Pharmaceuticals made a “$2.6-billion bet” on one of these startups, CRISPR Therapeutics, last November.[ii]  While many companies promise to revolutionize human health care, other biotech start-ups are focusing on using CRISPR in agriculture and for industrial production by microbes. The United States invested approximately $820 million dollars in synthetic biology research from 2008-2014, but less than 1 percent of these federal funds went to risk research.[iii]  While individual research projects at established institutions routinely undergo internal risk assessments, the federal government has invested little to monitor the biocontainment of synthetic organisms.  As the scale and the speed of genetic engineering increases dramatically, bioartists are using molecular tools to explore hazards to public health and ecological communities.

Into the Weeds

The European Union instituted clear labeling guidelines for foods containing genetically modified organisms (GMOs) in 2003—creating a policy with the intent of protecting “human and animal health and the environment.”[iv]  As a deep divide emerged between Europe and the US government on this issue, an artist collective initiated a project on biotechnology since they felt it was “one of the most misunderstood areas of production in the cultural landscape.”  The Critical Art Ensemble set up mobile laboratories throughout Europe in 2003-2004 where members of the public could test their groceries to see if the ingredients had been genetically modified.  DNA primers and a technique called polymerase chain reaction enabled the artists to hunt for GMOs in processed foods without any labeling.  This project, Free Range Grain, had widely variable results: in Holland all of the unlabeled foods tested were GMO-free, while in Austria 100% of unlabeled foods contained GMOs.  Foods that tested positive were labeled as such and offered to the public for consumption in art galleries.[v]

Free Range Grain provoked discussion about the difficulties of regulating biotechnology in a global legal landscape.[vi]  “You can ban GMOs,” said Steve Kurtz, a co-founder of Critical Art Ensemble, “but that doesn’t mean that they aren’t coming.”  With this project Kurtz aimed to catalyze public debate about scientific evidence of the harms and benefits of genetic engineering.  The widespread use of transgenic crops in agriculture has been driven by a variety of potential benefits, including increased yields, easier and more effective weed/pest control, lower prices to consumers, a wider variety of produce available throughout the year, and the production of nutrient-enriched staples.[vii]  But there are also scientific findings about problems created by genetically modified organisms already on the market and in the wild.

Members of the public who tested their groceries at the Free Range Grain exhibit had the opportunity to learn about gene flow from genetically modified crops to their wild relatives.  The Critical Art Ensemble brought attention to a variety of Roundup Ready crops which were created by Monsanto to tolerate glyphosate, the active ingredient in Roundup brand-name herbicide.  Glyphosate has been classified as “possibility carcinogenic to humans” by the World Health Organization.[viii]  Initially Monsanto argued that Roundup Ready crops would reduce the need for conventional pesticides.  Canola plants (Brassica napus), which were engineered to be Roundup Ready by Monsanto, have the ability to hybridize with two other species in the genus Brassica, wild radishes (Raphanus raphanistrum), and many other weedy mustard species.[ix]  Weeds, with transgenes giving them resistance to Roundup, have emerged from hybridization.[x] Increasingly toxic herbicides are now used to kill these transgenic weeds—both ecological and public health problems have resulted.[xi]

Another modified food discussed in the Critical Art Ensemble exhibit, corn with genetic material from the bacterium Bacillus thuringiensis (Bt), has been linked to the mortality of butterflies and beneficial insects.  Genes coding for Bt toxins were inserted into corn plants to protect them from pests.  But a study of Bt corn, published by the journal Nature in 1999, found that “transgenic pollen harms monarch larvae.”  Monarch butterfly caterpillars reared on milkweed leaves dusted with pollen from genetically modified corn, according to this study “ate less, grew more slowly and suffered higher mortality than larvae reared on leaves dusted with untransformed corn pollen or on leaves without pollen.”[xii]

The Bt corn plants used in the 1999 Nature study were manufactured by Novartis Seeds, a company based in Basel, Switzerland.  Responses to the monarch butterfly research, from Novartis and other industry groups, were defensive at first.  Life science companies criticized Nature for publishing a paper that was “premature, incomplete, and unconvincing.”[xiii]  Controversy about Bt corn causing harm to non-target organisms was artificially maintained with some of the same tactics that oil companies have used to maintain controversy about climate change.  One now-defunct website, www.bio-scope.org, questioned the research methods and raised concerns about the political use of science.[xiv]  A subsequent scientific study, funded by industry groups, later suggested “that the impact of Bt corn pollen from current commercial hybrids on monarch butterfly populations is negligible.”[xv]

Potential harms of Bt have been studied in a handful of other insect species—like beneficial predatory lacewings[xvi]—but it is unknown if these transgenes are one of the factors contributing to the dramatic decrease of invertebrate populations worldwide.[xvii]  “On the butterfly issue we saw many more problems with Round Up, because it kills all the plant life,” said Steve Kurtz, the co-founder of the Critical Art Ensemble.  “Milkweed likes to grow around crops,” Kurtz said. “If you ever go to a place where there is massive monocrop GMO cultivation the ecosystem is just ruined, it is destroyed.”

The Critical Art Ensemble wanted to bring their Free Range Grain exhibit to the United States to test unlabeled foods for GMOs.  But the artist collective was shut down in a dramatic action by Homeland Security and the Joint Terrorism Task Force in 2004.  FBI agents raided the home of Steve Kurtz in Buffalo, New York—seizing his laboratory equipment, including a PCR machine he had been using to test for genetically modified sequences.  Kurtz’s wife had unexpectedly died in her sleep on May 11^th, 2004.  While the Erie County Medical Examiner’s Office ruled that she died of natural causes, paramedics had become suspicious when they found petri dishes with live E. coli bacterial cultures and scientific equipment in the couple’s home.[xviii]  Initially Kurtz was detained on suspicion of “bioterrorism,” but after a costly and prolonged courtroom battle he was cleared of all charges.

While the Critical Art Ensemble was using a harmless strain of E. coli for an art project, someone with malicious intent could theoretically manufacture harmful bacteria relatively cheaply.  E. coli are part of the normal human gut flora and are readily available to artists or hackers through biological supply companies.  Some strains of E. coli are virulent—producing diarrhea, fever, bloody stool, and, in rare cases, death.  Someone with a DIY CRISPR kit could technically make custom DNA sequences from known pathogens and insert the genes into their organism of choice.

Safeguards are in place to prevent citizen scientists from inadvertently working on pathogens, according to Emily Leproust, the CEO of Twist Bioscience—a company based in San Francisco that offers gene synthesis to commercial customers.  Synthetic biology companies generally use a two pronged screening processes: customers are vetted and gene sequences are checked against a database of harmful organisms.  All customers who order DNA sequences from Twist Bioscience are checked against government lists of unauthorized individuals and entities, including the Specially Designated Nationals (SDN), the Debarred Denied Persons, Entity, and Unverified lists, as well as the German government Handbuch der Deutschen Exportkontrolle.

Twist Bioscience performs automated screening using internally developed software to check ordered sequences against the Regulated Pathogen Database, which is curated by the IGSC (International Gene Synthesis Consortium).  Known pathogens of agricultural plants and animals—like Avian influenza, or foot and mouth disease—are included in the IGSC Database alongside human infectious diseases.  The IGSC Database is presently only available to companies in the Consortium and other researchers on a need-to-know basis.  An internal debate about publishing the IGSC Database is currently taking place.  One view within the Consortium, according to Leproust, is that “if you publish the database people will go poke holes in it—maybe we are adding too much, or maybe we are missing things.”

Currently there is not a formal mechanism that allows independent environmental scientists to submit organisms of concern for possible inclusion in the IGSC Database.  Some known pathogens, like the chytrid fungus that is responsible for the extinction of amphibians (Batrachochytrium dendrobatidis), might not be priorities for government regulators since they are not driving economic losses.  Twist Bioscience is ready to help set industry standards, says Leproust, by accepting submissions directly from the scientific community—going on and beyond the IGSC standards, to add organisms of possible concern to their internal database.

Mutants Escape

While FBI actions against the Critical Art Ensemble had a chilling effect on the bioart world, many artists continue to explore the creative and critical potentials of biotechnology.  Adam Zaretsky, a bioartist whose work questions the manipulation, objectification, and instrumentalization of other organisms, has already ordered a DIY CRISPR kit from the Indiegogo campaign.  “Bipolar Flowers,” Zaretsky’s 2012 artwork, used zinc finger nucleases to “reprogram” the genome of mustard plants, giving the public an opportunity to consider how laboratory protocol routinely upregulate and downregulate hundreds of gene suites.  In using CRISPR to make similar artworks, Zaretsky plans to explore “great hopes invested in the products of genetic engineering” alongside “biophobic visions of environmental apocalypse.”

Genetically modified organisms have already escaped as a result of Adam Zaretsky’s art practice.  In 2001 he inadvertently released some “antennapedia” fruit flies—a common lab strain with legs growing out of their heads instead of antennae—triggering a heated debate on the campus of San Francisco State University, where he was a Visiting Professor.  After a firestorm of e-mails from the local University Animal Care and Use Committee, fruit fly geneticists from top laboratories weighed in on the situation.  “The mutation that causes the antennapedia phenotype, while induced by mutagenesis in the lab, can, in theory occur naturally in wild populations,” wrote Brad Jones from the NYU Medical School in an e-mail.  “You must realize that such a mutation is actually quite detrimental to the fly and will ultimately not propagate through the population, as a fly carrying such a mutation will be at a major disadvantage, and natural selection will quickly remove it.  In fly labs, flies get loose all the time.”  Chiming in on the same thread, John Locke of the University of Alberta wrote: “You can eat them and there is no danger.  We often find them in our coffee cups and sometimes not (it was too late – down they go).”[xix]

Organisms routinely escape from established laboratories.  The controversy stirred up by Adam Zaretsky’s artwork brought attention to the fact that containment protocol for genetically modified organisms are far from perfect.  Government authorities are usually quick to intervene when risks to human health emerge from laboratory facilities.  When inspectors found live anthrax spores outside a US Army containment area in September 2015, the Department of Defense froze operations at nine biodefense laboratories where work is done on dangerous pathogens.  U.S. federal funding for synthetic biology prioritizes defense initiatives, but support for monitoring environmental risks lags far behind.[xx]

Transgenes can spread through populations relatively quickly, provided that the genes offer fitness advantages.[xxi]  While debilitated flies with legs growing out of their heads are unlikely to spread in the wild, mutant alleles with neutral fitness consequences can randomly drift through populations.[xxii]

Drought-tolerant corn and other crops resistant to blights are being created by DuPont Pioneer in collaboration with Caribou Biosciences, a company co-founded by CRISPR pioneer Jennifer Doudna.  Caribou has already raised $11 million in initial funding to use gene editing tools for medical therapy, industrial chemical and enzyme production by microbes, as well as agriculture.  Corn and wheat plants edited with CRISPR are already growing in greenhouses and will be planted in field trials this spring.[xxiii]  “Precision breeding technologies have the benefit of being able to introduce naturally occurring, valuable traits much faster and more precisely than using traditional breeding methods,” said Andrew May, Caribou’s Chief Scientific Officer.  In contrast to the regulations that govern the sale of earlier genetically modified organisms, like Bt corn, the US government might decide to not regulate products made with CRISPR before they go to the market.

The Centaur is Not Out of the Barn

According to Henry Greely, a bioethicist at Stanford University, “the centaur has left the barn.”[xxiv]  Laws in the United States currently focus on regulating the products of genetic engineering, rather than the process.  Changes might be made to the regulatory framework to prevent bioartists from seeking “fame through sometimes shocking transgressions,” in the words of Greely.  Since molecular tools are already in the hands of artists, Greely says that regulatory cracks should be quickly shored up before wild “CRISPR critters” emerge.[xxv]  Greely is not alone in calling for new laws to regulate gene editing processes, not just the products.  Outside of the United States many leaders are more concerned about commercial enterprises, rather than “shocking transgressions” by artists.  The United Nation’s Convention on Biological Diversity has formally urged member states to regulate synthetic biology to ensure that activities in one country cannot harm the environment of another.  A 2014 UN declaration, which was supported by 194 nations, called for the establishment of new protocol to scientifically assess risks to biodiversity as well as human health, food security, and socio-economic systems.[xxvi]

Nations without strong biotechnology industries—like East Timor, Ethiopia, and Bolivia—were pushing for an even stronger UN declaration.  These countries called for a complete moratorium on the release of synthetic organisms, saying that new products could replace agricultural commodities and devastate their economies.[xxvii]  CRISPR has the potential to exacerbate inequality along lines of race, class, and gender, according to Charis Thompson.  Underserved groups in powerful countries, and whole nations that are structurally marginalized in the global economy, might not enjoy the benefits of CRISPR even as they are exposed to environmental and health risks.  “It is important to encourage bioart and biohacking beyond the ‘garage’ which tends to be associated with the same white masculine competitive start-up ethos as the dominant tech industry,” Thompson said.

Since it is relatively difficult to engineer organisms that can actually thrive in the wild, biosecurity risks are less likely to emerge from low-budget hackers but instead from large-scale commercial ventures.  Even if databases can help protect public health and the environment from known pathogens, it is difficult to safeguard against the unknown as transgenic organisms accidentally escape from laboratories.  Genetically modified plants are already hybridizing with wild relatives with unpredictable results.  As thousands of foreign genes are inserted into E. coli bacteria with CRISPR these novel “biohacked” strains have the potential to accidentally escape into the wilds of the human microbiome.

Unified international laws will likely not be developed for synthetic biology, if climate change negotiations are to serve as a guide.  But, instead we will hopefully see thousands of small precautionary decisions by regulators, university ethics committees, bench scientists, and communities of hackers.  Centaurs are not running wild yet, and actions are being taken so that citizens are not left to chase after escaped Frankenstein monsters with torches.  Artists and citizen scientists are helping create an arena for the public to face an emergent transgenic reality.  Rather than fear bioartists with CRISPR kits, the scientific community is starting to appreciate their critical contributions to our shared cultural archive.

 

Eben Kirksey has published two books with Duke University Press—Freedom in Entangled Worlds (2012) and Emergent Ecologies (2015)—as well as one edited collection: The Multispecies Salon (2014). Eben studies the political dimensions of imagination as well as the interplay of natural and cultural history.  Writing in collaboration with Stefan Helmreich he coined the term “multispecies ethnography” to describe new approaches for studying contact zones where the lines separating nature and culture have broken down. Eben Kirksey holds a three-year DECRA fellowship from the Australian Research Council which is enabling his work in Europe, the Americas, and the Pacific (2014-2017). He is a permanent faculty member in the Environmental Humanities program at UNSW. Currently he is Princeton University’s 2015-2016 Currie C. and Thomas A. Barron Visiting Professor, where he is researching and writing a new book.

References

[i] Baker, S. Tate Magazine, 26, 42-7 (September 2001).

[ii] Maxmen, A. Wired, 23, 62 (August 2015).  See also: http://www.fool.com/investing/general/2015/11/07/vertex-pharmaceuticals-26-billion-bet-on-crispr.aspx

[iii] Wilson Center Report on U.S. Trends in Synthetic Biology Research Funding (Kuiken, 2015).   Available on-line: https://www.wilsoncenter.org/publication/us-trends-synthetic-biology-research-funding

[iv] Fact Sheet: EU’s Policies on GMOs (EU, 2015).  Available on-line: http://europa.eu/rapid/press-release_MEMO-15-4778_en.htm

[v] Kelley, L. BioArt Kitchen (I.B. Tauris, 2016), 101.

[vi] Artist Statement: Free Range Grain (Critical Art Ensemble, 2004).  Available on-line: http://www.critical-art.net/FRG.html

[vii] Chapman, M. A. & Burke, J. M. New Phytol, 170, 430 (2006).  

[viii] IARC Monographs. 112 (WHO, 2015).  Available on-line: http://www.iarc.fr/en/media-centre/iarcnews/pdf/MonographVolume112.pdf

[ix] Chapman, M. A. & Burke, J. M. New Phytol, 170, 436-7 (2006); Schafer, M. G. et al. PLoS One, 6, e25763 (2011).

[x] Londo, J. P., Bautista, N. S., Sagers, C. L., Lee E. H., Watrud, L. S., Ann Bot, 106, 957-65.

[xi] Landrigan, P. J. & Benbrook, C. N Engl J Med, 373, 693-695 (2015).

[xii] Losey, J. E., Rayor, L. S., Carter, M. E. Nature, 399, 214 (1999).

[xiii] Hodgson, J. Nat. Biotechnol. 17, 627 (1999).

[xiv] Murphy, J.,  Levidow, L. & Carr, S. Social Studies of Science, 36, 133-160 (2006).

[xv] Sears, M. K. et al. PNAS 98, 11937-11942 (2001).

[xvi] Meissle, M., Zund, J, Waldburger, M., & Romeis, J. Scientific Reports, 4, 5900 (2014).

[xvii] Dirzo, R. et al. Science, 345, 401-406.

[xviii] Baard, M. Wired (2004).  Available on-line: http://archive.wired.com/medtech/health/news/2004/06/63637?currentPage=all

[xix] Zaretsky, Workhorse Zoo (2001).  Available on-line: http://www.emutagen.com/downloads/TomeofEmailwzooEthics.txt

[xx] https://www.wilsoncenter.org/publication/us-trends-synthetic-biology-research-funding

[xxi] Chapman, M. A. & Burke, J. M. New Phytol, 170, 437.

[xxii]  Kimura, M. Nature 217, 624-6.

[xxiii] Regalado, A. MIT Biotechnology Review (2015).  Available on-line: http://www.technologyreview.com/news/542311/dupont-predicts-crispr-plants-on-dinner-plates-in-five-years/

[xxiv] Dowd, New York Times, (May 7, 2005).  Available on-line:  http://www.nytimes.com/2005/05/07/opinion/what-rough-beasts.html?_r=0

[xxv] Charo, A. & Greely, H. The American Journal of Bioethics 15, 13 (2015).

[xxvi] Convention on Biological Diversity, Decision XII/24 (2014).  Available on-line: https://www.cbd.int/doc/decisions/cop-12/cop-12-dec-24-en.pdf

[xxvii] http://www.synbiowatch.org/2014/10/regulate-synthetic-biology-now-194-countries/