Difference between revisions of "Team:UC Davis/Human Practices"

Introduction

A guiding theme which we returned to again and again, as we designed our project, was the awareness that science does not happen in a vacuum. Science and technology exist within social frameworks– public policy, economics, public opinion, and overall acceptance of a new innovation are crucial factors to consider. A well researched, well tested product can and will fail the essential test of “usefulness” if external social factors are disregarded. A product that the public will not accept and use is a poorly designed product. This is especially true within the field of synthetic biology.

The iGEM guidelines for human practices specify that teams must carefully consider whether their work is useful and good for the world. As we learned through the course of our project, it is important to be aware of the context in which a product is used. We found that a “good” product is only good within a narrowly defined set of boundaries, insofar as it is useful to a specific person or group of people, at a specific time and place, and that the use to which it is put is not harmful.

For a simple example, let us consider the case of a fishing pole. A fishing pole is useful in some cases– at a lake or stream– but useless in other cases– such as in a desert or in a fancy restaurant. Furthermore, a fishing pole will be useless to a vegetarian person who does not believe that it is ethical to catch and eat fish. Additionally, a fishing pole may be used to capture and eat an endangered species of fish, causing harm to the environment. It is important to note that although the minimal set of conditions necessary for which a fishing pole could be successfully used (e.g. presence of fish in an adequately sized body of water) are met in some circumstances, this is no guarantee that it would be appropriate to use the fishing pole in those circumstances. If you pull out a fishing pole in a world renowned aquarium such as the Monterey Bay Aquarium, you will be asked to never come back. In none of these cases does the “goodness” or “usefulness” of the fishing pole depend directly on the physical design and composition of the device, or even whether the device functions as intended, but entirely on the context in which the device is used.

Taking a step back, returning to the field of biotechnology, there are many examples in which products or services were offered or presented in ways which were incompatible with maintaining public trust. Among these are cases of pharmaceutical executives arbitrarily increasing the prices of lifesaving therapeutics by factors of several thousand percent, or the famously unpopular patents of Genetic Use Restriction Technologies (GURT), better known as “terminator genes,” which would prevent farmers from reusing seed stocks for multiple generations [1].

According to Pew Research Center, 39% of Americans say that genetically modified (GM) foods are worse for their health, compared to non-GM foods [2]. According to a 2016 Gallup Poll, 51% of Americans have a negative view of pharmaceutical companies [3]. “Big Pharma” and “Big Ag” are boogeymen that roll off the tongues of many Americans. And the stigma is even worse in other parts of the world.

Scientific Overview

Before diving deep into the human elements which we considered when designing our project, we would like to give a basic overview of what we built, as it will allow us to return throughout this guide to specific features and examine how human practices informed our decision making.

A Mammalian Cell Bioassay For Use In Environmental Toxicology

We designed a mammalian cell-based bioassay that reports activation of specific stress pathways via fluorescence, for use in environmental toxicology. To do this, we selected transcriptionally regulated target genes which are present in mammalian cells and are involved in stress pathways (see figure 1 below). We isolated the promoters with transcription factor binding sites from these target genes and coupled them to a fluorescent reporter gene. We selected EGFP, a variant of green fluorescent protein (GFP). GFP is ubiquitous in synthetic biology due to its reliability and ease of measurement [4]. EGFP is derived from GFP, and has been optimized for use in mammalian systems. When a chemical of concern is screened using our assay, it will trigger a specific stress response, and the reporter gene will be expressed, causing the assay to fluoresce. The fluorescence of the assay can be quantitatively measured and analyzed. This assay will provide data on the effect of chemicals of concern on the physiological health of mammalian cells; measurements may be easily taken a range of concentrations, durations of exposure, salinities, pH, temperatures, nutrient availabilities, and other conditions. This also allows for measurement of synergistic or interfering effects due to multiple chemicals of concern present simultaneously.

Figure 1: Selected Promoters and Stress Pathways

We selected promoter constructs derived from five target genes and coupled them to EGFP. These promoter and reporter gene constructs were inserted into a plasmid and transfected into two cell lines, originating in mice (AML-12) and hamsters (CHO-DG44), respectively. Our use of mammalian cell lines was under the UC Davis Biological Use Authorization (BUA) #R2565. The resulting bioassays were exposed to five different chemicals of concern at a variety of concentrations and conditions. Although human cell lines would make a superior model for human disease, compared to cell lines derived from hamsters and mice, for our project we chose not to use human cells, for reasons of safety, reproducibility by other teams, and the constraints of the competition.

A cell-based approach cannot replace in vivo toxicology studies. However these studies require extensive funding, time, and other resources. By developing a relatively low-cost, cell-based bioassay, preliminary data may be quickly gathered, allowing for more informed decision making as to which in vivo studies are necessary. By using a cell-based preliminary assay, it is our hope that researchers will be able to quickly gather data, make more informed decisions, and save resources. Our cell-based bioassay may also be used to add to the body of knowledge concerning the effect of specific chemicals of concern on the physiological health of mammalian cells and the mechanism of stress.

We chose to use mammalian cells because they make much more accurate models for human health than bacteria or yeast. Furthermore, within the iGEM competition and the field of synthetic biology as a whole, there has been relatively little work with mammalian systems, compared to bacteria, yeast, and algae. Working with mammalian cells brings a variety of new challenges and opportunities to iGEM: they are more difficult and expensive to culture than bacteria, they require specialized equipment and safety training, they can be used to produce proteins suitable for use in human therapeutics, they can be used for more complicated circuits and pathways utilizing spatial/temporal differentiation, and they are much more sensitive to chemicals in the environment (allowing for more sensitive biosensors and bioassays).

Environmental Overview

Our team chose from the beginning to pursue the environmental track of the iGEM competition. At the University of California, Davis, there is an established group of researchers who have been working with the EPA for the past 31 years to “acquire a better understanding of the human and ecological risks of hazardous substances; and advance the development of new technologies for the cleanup of contaminated sites” [11]. Our team had the opportunity to join UC Davis researchers on a trip to visit the Yurok People, a Native American tribe in Klamath, California who live on heavily polluted land.

The tribe have reported unusually elevated rates of cancer and miscarriage incidence, and have indicated they have reason to suspect that the cause may be tied to environmental pollution on their tribal land from local agricultural and forestry corporations. Researchers from UC Davis have been collaborating with the tribe’s scientists and governing council to gather data pertaining to environmental and human health.

The agricultural and forestry corporations in the region surrounding the tribe’s land are currently operating within legal regulations, however the tribe has indicated that these regulations are not as strict as they would like. One example a tribal member provided was that currently, herbicides may be applied within fifty feet of sources of drinking water. A concern is that this distance is not sufficient to prevent contamination of drinking water supplies. A variety of harmful chemicals have been found in the waters of the tribal lands, particularly microcystin toxins and organochlorine pesticides [12]. Analysis of water samples by the Young Lab at UC Davis in 2017 also found the presence of low concentrations of pharmaceuticals, including warfarin, in the waters of the tribal lands

We were informed by tribal members that the members of the tribe interact with the flora, fauna, and water of the region regularly. These interactions take forms including the consumption of seafood– particularly salmon and shellfish– harvesting local plants and processing them to make baskets, swimming in the river, and ceremonies involving locally harvested materials.

We selected several major environmental contaminants in the region for use in our project: copper sulfate, warfarin, 2,4-D, and metam sodium. These chemicals were selected based off their prevalence in the region, their negative impacts on human health, and the availability of use for our project. Additionally, we included hydrogen peroxide as a positive control, as it is easily obtained and causes oxidative stress to cells.

If the working hypothesis is found to be supported, that the tribe’s health crises are linked to environmental pollution of their lands and water, then the remedy would be to tighten regulations concerning the use of pesticides, herbicides, and other potentially harmful compounds. To affect such a significant policy change would require substantial scientific evidence, including careful in vivo studies. Our bioassay can serve as a tool with which to quickly and relatively cheaply acquire data which can be used to identity areas necessitating further study and inform which specific results to expect.

If this working hypothesis is not supported by further study, alternative explanations for the tribe’s health crises should be explored, including predisposing genetic factors within the population and other factors. This possible explanation– that the tribe may experience elevated rates of specific diseases due to genetic predisposition– was suggested during the visit to a member of the tribe’s scientific body by a member of our team, and elicited a surprising response.

The tribe’s scientist said that such a hypothesis would be very negatively received by the members of the tribe, for historical and cultural reasons. “It would be received,” the tribe’s scientist said, “as an attempt to blame the tribe’s health problems on an inborn deficiency of the members, which given the persecution and genocide which the tribe underwent in the nineteenth and twentieth centuries, would strike a very powerful and negative chord.”

The scientist went on to reference several well publicized cases in which geneticists have squandered the trust of indigenous communities [see 13 for additional commentary and further reading].

“Geneticists Have Squandered The Trust Of Indigenous Communities"

Cultural Context

When our team was invited to join fellow UC Davis researchers to visit the Native American tribe, we were given training in “cultural competency.” The purpose of this training was to educate the researchers, who as science professionals, had varying degrees of experience dealing with other communities, how best to behave to ensure that the tribe was treated with respect as a partner in research. The course was described in the prepared description of the site visit in the following manner:

“In this course, which will be preferably offered on-site in Yurok Country and feature YTEP and other Yurok tribal presenters, university researchers will be trained on tribal sovereignty, tribal intellectual property rights, trial history, tribal land and water rights, and on building effective collaboration with tribes. While the focus will be on working with the Yurok Tribe, the principles taught will be applicable to collaboration with other tribes and indigenous nations in the US and globally.”

At the site visit, the other researchers and our team were taught some of the history of the tribe by a member of the tribal leadership council. We were also taught some of the customs, values,and ceremonies of the tribe, particularly regarding the strong cultural connection between the members of the tribe, the land of the region, and the native flora and fauna.

The team of UC Davis researchers included professors of Native American studies who helped the other researchers in questions of best practices regarding cultural competency in the course of their research. A key point of best practices we were told was to never claim the authority to say what another group does or does not believe, unless it is approved by or previously expressed by an authority of the group. For example, it would not be acceptable to write on our iGEM wiki without sources: “the (blank) tribe believes (blank), therefore...” Any claims made about the beliefs or opinions of another group should be thoroughly grounded in verifiable evidence that the group does in fact hold these beliefs. For example, a claim may be supported by quoting a resolution or law passed by a body such as a tribal leadership council or another authorized body.

At the first meeting, our team introduced ourselves to our fellow researchers, the tribe’s principal investigator (PI) working on environmental toxicology, and members of the tribe. After we explained who we were and what the iGEM competition was, the tribe’s PI said that she was familiar with some work being done regarding synthetic biology and bioremediation, and that a project involving release of genetically modified organisms would not be acceptable to the tribe. The iGEM competition as a whole has strict “NO RELEASE” rules, however many projects are designed in such a way that the ultimate use-case for their product would require intentional release into the environment.

Through the course of the cultural competency training and the site visit as a whole, a theme that resurfaced many times was a history of the tribe being taken advantage of by outsiders. Possibly due to this, several of the tribal members expressed skepticism of the intentions of outsiders. To paraphrase a comment made by a tribal member, “Plenty of people come to a tribe from a fancy university promising to fix things, and then they publish a few papers, get a few more letters after their name, and leave, but the problems haven’t gone away.” We were duly aware of this sentiment throughout the site visit, and took measures to ensure that we did not promise anything we could not fulfill, given the limited time and resources of the iGEM competition.

An indigenous peoples’ publication which is not connected with the Yurok Tribe, Third World Network, published an essay several years ago, titled “Biotechnology and Indigenous Peoples.” In the essay, the author, Victoria Tauli-Corpuz, expresses the following position, regarding the relationship between indigenous peoples and biotechnology:

“Biotechnology carries with it a worldview or philosophy which is reductionist and determinist. A living organism is reduced into its smallest component, the gene. The explanation of the way the organism behaves is sought in the genes. This worldview also regards nature as something which should be controlled, dominated, and engineered or re-engineered.

Should Nature Be Engineered?

This runs counter to indigenous beliefs, knowledge, and practice. The cosmological vision of most indigenous peoples regards nature as divine and a coherent whole, and human beings as a part of nature. Thus, it is imperative that humans should create meaningful solidarity with nature. This is the “web of life” concept or what is now referred to as the ecosystem approach which appreciates the relationship and bonds of all of creation with each other. Human beings have to work and live with nature and not seek to control and dominate it. Whether we recognize it or not, we humans are totally dependent on water, air, soil, and all life forms and the destruction or pollution of these will also mean our destruction. The integrity or intrinsic worth of a human being, plant, or animal is measured in relation to how it affects and relates with the others.

For indigenous peoples, biodiversity and indigenous knowledge or indigenous science cannot be separated from culture and territoriality. Thus, the genetic determinism of biotechnology conflicts with the holistic worldview of indigenous peoples.” [14]

Although the author of this essay should not be construed as an authorized spokesperson for every indigenous group, the perspective she puts forward is worth careful consideration by iGEM teams who plan on engaging with an indigenous community. That being said, it is important to remember that it would be a key mistake to assume you understand the beliefs of a specific indigenous group by generalizing from a publication such as this essay, and that it is essential to listen carefully and ask respectful questions in order to find out how a specific indigenous group actually feels about biotechnology.

Keep in mind that there are many positions and subtleties between “pro-biotechnology” and “anti-biotechnology.” We experienced this while interacting with the Yurok Tribe: the tribe has expressed in legislation that some areas of biotechnology are unacceptable– for example, transgenic salmon aquaculture– while other areas of biotechnology are acceptable to them in certain contexts, including production of pharmaceuticals and well regulated biomedical research [15].

Upon requesting clarification regarding the Yurok Tribe’s stance on biotechnology, a member of the tribe’s scientific body told us that while it is against the Tribe’s constitution and traditional environmental stewardship practices to work to inherently change the nature of ecosystems or species within it, work with biotechnology in set parameters and using science to inform traditional practices and management is acceptable. The tribe’s scientist concluded by saying that much of the issue is over setting appropriate boundaries in which biotechnology may be used.

Political/Legislative Context

In the United States, recognized Native American tribes are self-governing bodies, and have the power to make and enforce laws and regulations on their own lands. The specific Native American tribe which we visited, the Yurok People, have expressed their position on genetic engineering in an ordinance adopted in 2015, which may be accessed here [15].

In the ordinance, the tribe makes clear that they view the release of genetically modified organisms into their environment to be a major threat to their cultural values and traditional way of life. Compared to the United States as a whole, which has relatively tolerant laws regarding the production and use of genetically modified organisms, the tribe has far stricter laws.

The Tribe Has Far Stricter Laws about GMOs Than The United States

Interestingly, within the ordinance, the tribe makes several exceptions. The first is particularly unusual: “Genetically engineered or modified organisms do not include organisms created by traditional selective breeding, [...] or microorganisms created by moving genes or gene segments between unrelated bacteria” [15]. As much of biotechnology and synthetic biology uses bacteria as a host, we were surprised to find that the ordinance deemed the majority of the work done in the iGEM competition as acceptable. It is however worth noting here that we chose to work with mammalian cells, rather than exclusively bacterial cells, a point we will revisit in the next section.

The ordinance also provides exceptions to the prohibition for “state or federally licensed medical research institutions, medical laboratories, or medical manufacturing facilities engaged in licensed medical production, or medical research involving genetically engineered or genetically modified organisms,” as well as for, “educational or scientific institutes” [15]. This makes it appear that the major focus of the ordinance is to restrict agricultural biotechnology firms and their crops/livestock on tribal lands. The ordinance specifically refers to transgenic salmon– which are referred to as a threat to their way of life– and the significance of the wild salmon to the tribe’s cultural values.

Shortly after the genetic engineering law was passed by the Yurok Tribe, a local (non-Yurok specific) publication, the Del Norte Triplicate, published an article titled, “Yurok Tribe: GMO Food Production Banned.” In the article, several tribal leaders were interviewed regarding the new law:

“Yurok Chief Judge Abby Abinanti said it is an inherent, and now codified, tribal sovereign right ‘to grow plants from natural traditional seeds and to sustainably harvest plants, salmon and other fish, animals, and other life-giving foods and medicines… as we have successfully done since time immemorial.’ [...]

[Tribe Chairman James] Dunlap said the council's action was based on unanimous support from members both on and off the reservation. [...] ‘This Ordinance is a necessary step to protect our food sovereignty and to ensure the spiritual, cultural and physical health of the Yurok People.’” [16]

We carefully considered the position taken by the tribe, concerning the introduction of genetically modified organisms as a threat to their cultural values and traditional way of life. While many arguments made by opponents of GMOs focus on perceived threats to human health, which can be settled empirically by careful in vivo studies, cultural arguments cannot be easily dismissed. A community should have the right to live according their values and uphold traditional ways of life. If certain communities decide that their values are incompatible with the introduction of genetically modified organisms on to their land, then their decision should be respected.

The visit with the Yurok tribe helped us become aware of different sets of legal frameworks in which we operated. While working on the campus of our university, we were subject to federal (America), state (California), and local (Yolo County, City of Davis, University of California) laws. Through the course of our research, we were surprised to find out that many counties in California have laws banning the use of GMO-crops for agriculture. If we were to return to test our device on tribal lands or in another community with strict local policies regarding biotechnology, we would be required to follow their specific ordinances and regulations, such as seeking prior written permission from the Yurok Tribe’s leadership council to use genetically engineered devices for biomedical research on their land. Likewise, it would be necessary to seek prior written permission before testing environmental samples taken from tribal lands. A similar procedure would be required when working with other communities.

How We Proceeded

From the beginning, our team chose to pursue the environmental track of the iGEM competition. This is due in part to the culture of Davis, California. In the small college town of Davis, the community’s most distinctive values are commitment to environmentalism, education, and inclusiveness. This has carried over onto the University of California campus, a school with top-tier programs in the life sciences, medicine, and engineering. At UC Davis, researchers actively seek out solutions to the ongoing environmental crisis. We chose to capitalize on the wealth of knowledge and expertise available to us by designing a project involving environmental toxicology

Many past iGEM teams have designed new solutions to environmental problems involving bacterial biosensors as well as in situ bioremediation via release of transgenic bacteria. Although iGEM has strict “NO RELEASE” rules during the course of the iGEM competition, many such projects are designed in such a way that the ultimate use-case for their product would require intentional release into the environment. After interacting with the Yurok Tribe it became immediately clear that many communities, especially many indigenous communities, would firmly object to any project involving intentional release, which effectively ruled out in situ bioremediation as an area for our project.

Our team’s visit with the Yurok Tribe helped us to focus our project, as it gave us concrete data and a well defined problem with which to work with. We designed our bioassay to be an “intracellular sensor” rather than an “intercellular sensor.” By this we mean that our bioassay is not designed to indicate presence/absence of specific chemicals of concern in the environment, but rather how mammalian cells respond to environmental samples. We researched physiological stress pathways in mammalian cells which are activated by environmental stressors. We chose to design our bioassay in this way, so that it detects a phenomenon (e.g. activation of an oxidative stress pathway) rather than a chemical (e.g. dioxin) because many tools already exist which enable scientists to detect chemicals in the environment. The Yurok Tribe’s working hypothesis, you will recall, was that even low levels of chemicals of concern cause damage to animals and people. By developing an assay that is able to report activation status of physiological stress pathways, data may be gathered to either support or refute this hypothesis.

To determine which stress pathways are the most relevant, we examined published literature regarding chemicals of concern in the Klamath region. We selected 2,4-D, warfarin, copper sulfate, metam sodium, and hydrogen peroxide, as representative chemical inducers of the major relevant forms of physiological stress. Recall that our bioassay is not designed to detect chemicals of concern, but rather the stresses they inflict on cells. As such, all of our chemicals of concern served as positive controls because they are known to inflict stress on cells at a certain concentration. The question we sought to answer was what the effect of these stress inducing chemicals at low concentrations.

After we had selected our stress pathways and the chemicals of concern associated with them, we searched through published literature for genes in stress pathways in animals which were known to be transcriptionally induced by these chemicals. This search provided us with two genes in the Metallothionein family, two genes in the Growth Arrest and DNA Damage family, and a gene in the Fibroblast Growth Factor family (see figure 1, page 5).

We used mammalian cells for our bioassay. The cell lines we used were originally from chinese hamsters (Criteculus griseus) and mice (Mus musculus). Before we began work with these cell lines, we acquired a Biological Use Authorization (BUA) from our university (UC Davis BUA #R2565). Our cell lines were acquired from ATCC [17]. The Yurok Tribe’s genetic engineering ban has generous exemptions, including all of bacterial synthetic biology. Had we chosen to work with bacteria exclusively, we would have had far greater legal freedom in this specific circumstance, however we found compelling reasons to work with mammalian cells.

Mammalian cells make much more accurate models for human health than bacteria or yeast. As we learned through the course of our project, an ongoing, open question in the field of environmental toxicology and indeed biology as a whole, is “how good of a model for human health are lab rats?”

How Good Are Animal Models? Or Any Model For That Matter?

There are fundamental assumptions made in even the most meticulous in vivo studies that the chosen model organism will provide accurate data pertaining to human health. And as long as our society (rightly) places limits on human experimentation, this question will remain relevant. Although answering detailed and subtle questions about which animal model best balances scientific and ethical considerations is beyond our capabilities, it is readily apparent that humans and hamsters share far more physiology in common than humans and bacteria, which are billions of years of evolutionary history distant from us

Our bioassay could be applied in many other circumstances beyond just this one region in northern California, however we became very interested in how a project such as ours would be carried out in a community with strict laws regarding biotechnology. With respect to this, we researched the local laws and sought out commentary in local publications and by speaking with tribal members, in order to understand how the legal context for biotechnology was connected to the cultural and historical contexts in this community. We also sought out more general accounts of the relationship between indigenous communities and biotechnology, written by members of indigenous communities, not outsiders. This allowed us to place the specific details of our interaction with a single Native American tribe in California within a larger context.

Lessons Learned

In California, many local communities have enacted much stricter laws regarding biotechnology and GMOs, compared to the federal standards. In addition to Native American tribes such as the Yurok People, the counties of Marin, Mendocino, Santa Cruz, Sonoma, Trinity, and Humboldt have all banned the use of genetically engineered crops [18]. It is our hope that some of the principles we learned from interacting with the Yurok Tribe can be applied in other situations where iGEM teams interact with communities who have concerns about biotechnology.

The most important principle, we learned, was to listen first. By giving the community a chance to speak for themselves, we were able to actually understand what they felt and believed, rather than rely upon our own flawed assumptions. After listening, we asked questions about certain topics we wanted further clarification of. We took the time to read through the community’s local laws and regulations, and tried to make sense of elements we found unusual, such as large exceptions for microbiology in a genetic engineering ban. We read through articles and editorials in local publications, trying to make sense of interconnected political and cultural threads.

We also learned to resist the urge that many iGEM teams have, to act as evangelists of bioengineering.

It is not the purpose of the human practices component of iGEM to convince other people that synthetic biology is the answer to all of their problems.

Human Practices is Not The Same As Proselytism

There is a saying that “when you are holding a hammer, everything looks like a nail,” and this definitely describes many synthetic biologists, especially many students new to the field. We had to come to acknowledge that it only makes sense to use synthetic biology to solve a narrowly defined set of problems, and that part of that narrow definition includes the right cultural context. The goal of the iGEM competition is to build something useful using synthetic biology, and an unwanted product is a useless product.

We also found that it was necessary to consult experts in many fields, not just the most obvious ones. It was clear from the start that we would need to seek out experts in molecular biology, bioengineering, and environmental toxicology, but we also found it necessary to consult with experts in statistics, Native American studies, design, and hydrology. This allowed us to find out which questions we needed to ask about our project, how to build our device, and who would be using it.

We highly recommend iGEM teams who plan on interacting with indigenous groups to consult a professor or another expert in the relevant field and taking some version of “cultural competency training.” Through our cultural competency training, we learned some of the tribe’s history, culture, and values, and some best practices to ensure they were treated with respect as a partner in research. One of these key best practices was to never claim the authority to say what they do or do not stand for. Any such claim must be supported by a reputable, authorized source, such as a press release by a tribal leadership council or the text of a local law, ordinance, or resolution

We hope to see further respectful engagement and collaboration with indigenous communities in the iGEM competition in future years. Many of these communities face serious public health challenges, among other difficulties. The fields of synthetic biology and biotechnology provide powerful tools which may help resolve such crises in these typically marginalized communities, but only if developed in a responsible manner with input from the communities in question.

Works Cited

[1] "An Ethical Examination of Genetic Use Restriction Technologies." November 20, 2008. Retrieved September 26, 2018. http://www.ethique.gouv.qc.ca/en/assets/documents/OGM/TRUG/TRUG-avis-EN.pdf.

[2] Funk, Cary, and Brian Kennedy. “Public Opinion about Genetically Modified Foods and Trust in Scientists.” Pew Research Center: Internet, Science & Tech, Pew Research Center: Internet, Science & Tech, 1 Dec. 2016, www.pewinternet.org/2016/12/01/public-opinion-about-genetically-modified-foods-and-trust-in-scientists-connected-with-these-foods/.

[3] Gallup, Inc. “Restaurants Again Voted Most Popular U.S. Industry.” Gallup.com, 15 Aug. 2016, news.gallup.com/poll/194570/restaurants-again-voted-popular-industry.aspx.

[4] “PDB101: Molecule of the Month: Green Fluorescent Protein (GFP).” PDB-101, RCSB PDB, June 2003, pdb101.rcsb.org/motm/42.

[5] Larochelle, Olivier & Labbé, Simon & Harrisson, Jean-François & Simard, Carl & Tremblay, Véronique & St-Gelais, Geneviève & Govindan, Manjapra Variath & Seguin, Carl. (2008). Nuclear Factor-1 and Metal Transcription Factor-1 Synergistically Activate the Mouse Metallothionein-1 Gene in Response to Metal Ions. The Journal of biological chemistry. 283. 8190-201. 10.1074/jbc.M800640200.

[6] Santos, Anderson K. et al. "Expression System Based On An Mtiia Promoter To Produce Hpsa In Mammalian Cell Cultures". Frontiers In Microbiology, vol 7, 2016. Frontiers Media SA, doi:10.3389/fmicb.2016.01280.

[7] F.G. Schaap, A.E. Kremer, W.H. Lamers, P.L. Jansen, I.C. Gaemers. Fibroblast growth factor 21 is induced by endoplasmic reticulum stress Biochimie, 95 (2013), pp. 692-699, 10.1016/j.biochi.2012.10.019

[8] Li, Dahui et al. "Genotoxic Evaluation Of The Insecticide Endosulfan Based On The Induced GADD153-GFP Reporter Gene Expression". Environmental Monitoring And Assessment, vol 176, no. 1-4, 2010, pp. 251-258. Springer Nature, doi:10.1007/s10661-010-1580-7.

[9] Park, Jong Sung et al. "Isolation, Characterization And Chromosomal Localization Of The Human GADD153 Gene". Gene, vol 116, no. 2, 1992, pp. 259-267. Elsevier BV, doi:10.1016/0378-1119(92)90523-r.

[10] Mitra, Sumegha et al. "Gadd45a Promoter Regulation By A Functional Genetic Variant Associated With Acute Lung Injury". Plos ONE, vol 9, no. 6, 2014, p. e100169. Public Library Of Science (Plos), doi:10.1371/journal.pone.0100169.

[11] "UC Davis Superfund Research Program". UC Davis Superfund Research Program, 2018, https://www.superfund.ucdavis.edu/. Accessed 1 Aug 2018.

[12] Eagles-Smith, C.A., and B.L. Johnson, 2012, Contaminants in the Klamath Basin: Historical patterns, current distribution, and data gap identification: U.S. Geological Survey Administrative Report, 88 p.

[13] For a look at some of these cases, the following article references several of the most publicised times genetics researchers have lost goodwill with Indigenous peoples. “Ancient Genome Stirs Ethics Debate.” Nature News, Nature Publishing Group, www.nature.com/news/ancient-genome-stirs-ethics-debate-1.14698.

[14] “Ch. 21.15 Genetically Engineered Organisms | Yurok Tribal Code.” Yurok Tribe Tribal Code, Yurok Tribe, 10 Dec. 2015, yurok.tribal.codes/YTC/21.15.

[15]“Human Practices.” iGEM Foundation, igem.org/Human_Practices .

[16] “iGEM Medals.” iGEM Foundation, https://2018.igem.org/Judging/Medals .

Appendix

“The iGEM competition calls on students to build interdisciplinary teams of biologists, chemists, physicists, engineers, and computer scientists to ask new questions about what synthetic biology can do. Over the past ten years, thousands of students from countries around the world have started to imagine a future that uses biology as a design medium, and that relies on open-source, standardized parts to build novel biological functions.

iGEM teams "go beyond the lab" and imagine their projects in a social/environmental context, to better understand issues that might influence the design and use of their technologies. The most successful teams often work hard to imagine their projects in a social context, and to better understand issues that might influence the design and use of their technologies. Increasingly, they also work with students and advisors from the humanities and social sciences to explore topics concerning ethical, legal, social, economic, biosafety, or biosecurity issues related to their work. Consideration of these “Human Practices” is crucial for building safe and sustainable projects that serve the public interest.

Philosophy, Public Engagement / Dialogue, Education, Product Design, Scale-Up and Deployment Issues, Environmental Impact, Ethics, Safety, Security, Law and Regulation, Risk Assessment

Human Practices is a key component in the development of an iGEM project where teams consider the many ways that their research can impact society. The work that they do in this varies in many ways; some teams will question how synthetic biology could change our view of life and science, others will have an active dialogue with their community in order to assess the needs of the world around them and to educate the public about synthetic biology. Some teams have ventured into policy making by creating proposals to help advance the science in their country. Students have also developed educational resources in their language to teach younger and older generations about science, engineering, and biology. The safety and security risks are assessed by all teams as a competition requirement. They must actively consider how their project will affect their environment and how it will affect public perception.” [19]

“Convince the judges you have thought carefully and creatively about whether your work is responsible and good for the world. Document on your team wiki how you have investigated these issues and engaged with your relevant communities, why you chose this approach, and what you have learned. Please note that surveys will not fulfill this criteria unless you follow scientifically valid methods.""

See the Human Practices Hub for more information and examples of previous teams' exemplary work.” [20]