In the present article, I discuss key ecological and evolutionary questions that should be considered before such genetically engineered mice are released into natural habitats. 2019). After testing the efficacy of the most promising antibodies and various types of promoters to enhance gene expression, the team plans to design a resistance cassette, with multiple antibody-encoding genes. If all goes according to plan, the researchers hope to introduce the genetically engineered white-footed mice to Martha’s Vineyard and Nantucket within seven years. The project would still be years down the road. 2019). Giardina AR, Schmidt KA, Schauber ME, Ostfeld RS. Efforts to intervene and reduce human exposure to Lyme bacteria are complicated by a dynamic network of interacting species in this pathogen–vector–host community (Figure 2; Eisen et al. Some believe that the spread of this terrible disease was either as a … “If this works and we can actually modify mice so they are no longer reservoirs for Lyme disease in this model system we have in our own backyard,” Telford said. Therefore, results with lab mice suggest that GE production of subolesin antibodies may reduce tick feeding and transmission in white-footed mice, although this has yet to be determined. The research team also plans to initiate baseline ecological studies at all islands where GE mice would be released. 7 024001 View the article online for updates and enhancements. The measure of bird species occurrences is based on the Massachusetts Audubon Breeding Bird Atlas 2 (2007–2011, www.massaudubon.org). 2005), with examples of hypothetical, worst-case scenarios for the current case study involving GE Lyme-resistant white-footed mice. Huang C-I, Kay SC, Davis S, Tufts DM, Gaffett K, Tefft B, Diuk-Wasser MA. At my request, James led me down to the insectary where his lab at U.C. 2018a). Allison Snow (firstname.lastname@example.org) is a distinguished professor emerita of arts and sciences in the Department of Evolution, Ecology, and Organismal Biology at Ohio State University, in Columbus, Ohio. If transgenic chestnut strains receive regulatory approval, their introduced resistance genes will be able to spread freely via pollen and seeds into unmanaged habitats (NASEM 2019). The most common sign of infection is an expanding red rash, known as erythema migrans, that appears at the site of the tick bite about a week after it occurred. Lyme Disease is not unique to the United States, it appears all over the world. Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? In the near future, many other novel and more controversial applications of CRISPR-based genome editing in wild vertebrates are likely to be proposed, including the use of gene drives coupled with sterility genes to eradicate invasive pest populations (NASEM 2016, Harvey-Samuel et al. On coastal islands that lack populations of white-footed mice, Lyme transmission can occur because of other reservoir species such as the deer mouse, Peromyscus maniculatus (Isle au Haut, Maine; Rand et al. Therefore, separate GE founding populations representing the genetic diversity found on each island would need to be developed. 1986). Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, Nolan T, Crisanti A. Levi T, Kilpatrick AM, Mangel M, Wilmers CC. Specifically, CRISPR technology is easier to use than previous transgenic methods and allows researchers to delete, alter, or insert desired genetic sequences into known target sites of an organism's genome (Doudna and Charpentier 2014). Jones CG, Ostfeld RS, Richard MP, Schauber EM, Wolff JO. In an effort to encourage transparency and public oversight, the Mice Against Ticks project involves public meetings, media attention, and local steering committees that can recommend terminating the project on their island (Buchthal et al. There was once a Lyme disease vaccine sold in the US, yanked off the market only after a few years. 1991, LoGiudice et al. For example, if ticks are not able to feed on GE white-footed mice, information about whether this could lead to greater use of alternate hosts, including humans, or reductions in tick populations over time will be useful for evaluating possible benefits and risks. However, if the current trend continues, the number of “reported” cases could reach half a million in the next 10 years, but in reality this may actually mean millions! Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. 2018a, M. Pelikan and L. Johnson, personal communication). Deer and mice are some of the most common targets, but people are also unsuspecting victims. Their decision to do so provides a unique opportunity for professional ecologists and others to offer advice and contribute data that can be used to evaluate and address possible risks such as those described in the present article. This project involves engineering wild-caught white-footed mice to introduce two traits—resistance to the Lyme pathogen and, if feasible, resistance to feeding by the pathogen's tick vector. White-footed mice are regarded as a hub species within forest communities because of their key roles as consumers of seeds, invertebrates, and fungi, and as abundant small prey for many omnivores, carnivores, and scavengers (Figure 2; e.g., Ostfeld et al. 2017). Buchthal J, Evans SW, Lunshof J, Telford SRIII, Esvelt KM. Copyright © 2021 American Institute of Biological Sciences. This content was downloaded from IP address 188.8.131.52 on 25/04/2020 at 01:49 Search for other works by this author on: Box 1. For the current project, the first step is to engineer white-footed mice that constitutively produce antibodies to OspA and ideally also subolesin or another tick protein, using introduced antibody genes, promoters, and enhancers that will be derived from white-footed mice (Buchthal et al. Developing GE mouse lines that also are able to deter feeding by ticks may take longer, so I will not consider this trait for now. To promote rapid fixation within populations, the new gene can be inserted along with a gene drive system that causes biased inheritance of genetic elements and thereby ensures very high rates of transmission of the inserted gene to subsequent generations (Esvelt et al. Relationship between numbers of the endangered American burying beetle, Chain reactions linking acorns to gypsy moth outbreaks and Lyme disease risk, Editing nature: Local roots of global governance. L. lymegreen Well-known member. For the purpose of this review, I assume that it is possible to use genome editing to engineer white-footed mice with resistance to the Lyme spirochete. 2019). 2017). Even if white-footed mice with the GE resistance cassette can become established in the small-island field trials, ecological interactions on the larger islands of Nantucket and Martha's Vineyard could be complex, leading to uncertainties about how thoroughly the GE mice will be able to replace non-GE mice over time, and the extent to which populations of other reservoir host species could maintain the Lyme infection cycle on their own (Tsao et al. 2019). Ltd. Has Lyme Disease Been Engineered to Purposely Infect The Population? For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Doxycycline is the drug of choice for both diseases. Is it some attempt to reduce the population, an experiment, or simply a new tactic for drug companies to introduce some expensive cure at a later date? Nantucket could become the site of an unprecedented experiment to combat Lyme disease by releasing genetically modified mice on the island. Although white-footed mice are probably too small to serve as a breeding carcass for the federally endangered American burying beetle (Nicrophorus americanus), which has been reintroduced on Nantucket, adult burying beetles are known to feed on dead white-footed mice (Holloway and Schnell 1997, Mckenna-Foster et al. For example, key phenotypic differences between GE and non-GE white-footed mice might not become evident or consequential unless the mice are exposed to extreme environmental conditions, new parasites and pathogens, or certain predators or competitors. As with any ambitious, long-term research project, the research plan is likely to be modified as the work progresses, pending initial outcomes and benchmarks. The Environmental Protection Agency also could become involved if the GE white-footed mice are endowed with an antitick cassette and if this is viewed as a type of “pesticide” (NASEM 2017). Although regulatory agencies in the United States and elsewhere have little experience with such nonagricultural applications to date, many questions about potential environmental risks of releasing GE vertebrates are similar to those described in a position paper by the Ecological Society of America for all genetically engineered organisms (Table 1; Snow et al. Pages 18–47 in EDITORS, eds. Telford SRIII, Mather TN, Adler GH, Spielman A. Wolt JD, Keese P, Raybould A, Fitzpatrick JW, Burachik M, Gray A, Olin SS, Schiemann J, Sears M, Wu F. Oxford University Press is a department of the University of Oxford. 1) Lyme disease is endemic to all land areas surrounding Plum Island. University of Michigan Museum of Zoology Publication no. For those who are not familiar with this disease and are lucky enough not to be affected, they may be interested in reading an earlier article on this subject “Lyme disease explored with Les Roberts.” Les Roberts, who suffers from Lyme Disease, described it as “an all encompassing nightmare straight from the very pits of hell.” His experience with this disease encouraged him to write a book called “The Poison Plum” to help others better understand the dangers of Lyme Disease. FDA guidance no.187 states that discretionary regulation is based on asking “does the animal with intentionally altered genomic DNA pose any more of an environmental risk than its counterpart?” How this question is addressed and whether a formal environmental impact statement is required under NEPA (National Environmental Policy Act) appear to be case dependent (www.fda.gov, Meghani and Kuzma 2017). Like the American Academy of Environmental Medicine earlier this year, the LIA Foundation says there is more than enough evidence of harm in GM animal feeding studies for them to "urge doctors to prescribe non-GMO diets" and for "individuals, especially those with autism, Lyme disease, and associated conditions, to avoid" GM foods. 2) Many Lyme and Gulf War Illness patients are infected with the same genetically engineered organism (mycoplasma fermentens) created and patented by the US Government. 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