2019). 2018). This process represents the first phase of “problem formulation” used by regulatory agencies to evaluate GE organisms (e.g., Wolt et al. 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. Kevin Esvelt's group and others are working on nonglobal gene drives and other self-limiting approaches that are expected to be safer than global gene drives (Noble et al. Could genetically engineered mice reduce Lyme disease? Independent researchers who aim to evaluate possible hazards of releasing GE white-footed mice will need detailed information about the inserted genetic elements, including DNA markers for detecting the resistance cassette, the efficacy of these genetic alterations in conferring resistance, how the introduced GE mice differ from wild mice with regard to their genetic diversity, behavior, survival, and reproduction, and how the GE mice will be released (box 1). For example, CRISPR-based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). 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. 2005, NASEM 2016). Ideally, the introduced Lyme-resistant mice would be very similar to local white-footed mice in terms of their genetic diversity, physiological ecology, behavior, fitness, population dynamics, and ecological interactions in local habitats. Jones CG, Ostfeld RS, Richard MP, Schauber EM, Wolff JO. ''I'm here because I don't want to go through Lyme again,'' Ms. Kaufmann said as the genetically engineered vaccine entered her arm. To date, much of the scientific literature on expected risks of using genome editing and gene drives in wild species describes complications that could undermine success (i.e., the risk of failure), such as naturally occurring mutations that inactivate an introduced DNA sequence (e.g., Champer et al. In this lesson, students will watch the PBS NewsHour video, “ Could genetically engineered mice reduce Lyme disease? The US Department of Agriculture acquired the island in 1954 and established the modern-day Plum Island “Animal Disease Center” (PIADC), to safeguard against “foreign animal diseases” that could decimate the nation’s livestock (such as foot-and-mouth disease). Over time, this would reduce the prevalence of the disease. King looks at the ethics, and possible effects, of this prospect. 2019). 2008). “We’re making mice that are 100 percent white-footed mice, but can’t be reservoirs for tick-borne diseases,” Esvelt said. Nantucket could become the site of an unprecedented experiment to combat Lyme disease by releasing genetically modified mice on the island. Reprinted with permission from Levi and colleagues (2016). ''I don't mind being the Lyme vaccine poster child.'' Although a form of Lyme Disease has apparently existed for some time, many feel that the current version has undergone “changes.” In other words: genetic engineering. Anthropologist Barbara J. Thus, the name of the disease emerged. Within-population data could then be used to compare genetic profiles of current populations with subsequent populations after massive introductions of GE white-footed mice on Nantucket and Martha's Vineyard. Since I became involved in this subject, I have received many letters from others who suffer from Lyme Disease, and I am extremely grateful for their help in providing information for my articles. (b) Predators and competitors within the vertebrate host community, focusing on chipmunks, white-footed mice, and shrews, which serve as reservoir hosts for the Lyme spirochete (table 2). 2019). Previous investigators have examined many factors that affect the prevalence of spirochete-infected ticks, including small mammal populations that are highly variable in time and space, masting oaks (Quercus spp.) A key question of interest is whether GE Lyme-resistant white-footed mice will have altered fitness compared to their non-GE counterparts. The primary reason the plants are engineered … Under this scenario, which merits further investigation, smaller numbers of juvenile ticks would become infected with the spirochete over time, potentially crossing a threshold level that leads to lower infection frequencies in nonmouse reservoir species. Much will depend on the behavior and relative fitness of GE and non-GE mice and on the reservoir host use of blacklegged ticks, as is discussed below. On one site I found mention of an Iraqi scientist who worked on Plum Island in the 1980’s, apparently involved in biowar research. Buchthal J, Evans SW, Lunshof J, Telford SRIII, Esvelt KM. Resampling island and mainland populations using modern approaches such as whole genome sequencing combined with phenotypic data would be a useful starting point for reevaluating the extent of genetic divergence among these groups, as well as genetic diversity within populations (Ellegren 2014, Coates et al. 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. And Dr. Tim Lepore, a surgeon at a Nantucket hospital who has been seeing patients with Lyme since the ’80s, estimates that many more are infected than the … For example, CRISPR-based genome editing may be used to create white-footed mice (Peromyscus leucopus) that are resistant to the Lyme disease spirochete vectored by blacklegged ticks (Ixodes scapularis). Annals of the New York Academy of Sciences, Phylogeography and systematics of insular white-footed mice (, PhD Dissertation, Northeastern University, Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic, Promise and perils of gene drives: Navigating the communication of complex, post-normal science, Proceedings of the National Academy of Sciences, 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, Territorial behavior and populations of some small mammals in southern Michigan. In contrast to current transgenic crops or farm-raised transgenic fish, some future GE applications will focus on wild or feral species that will be able to reproduce and disperse freely in the environment. 3) Lyme Disease and Gulf War Illness share almost identical symptoms. Not every ecological or evolutionary question raised in the present article can be answered with empirical data, in which case modeling studies and extensive knowledge of relevant topics will be needed. The next extract provides a little more information on what APHIS does: “APHIS uses the term biotechnology to mean the use of recombinant DNA technology, or genetic engineering (GE) to modify living organisms. 1992, Buchthal et al. If the community were to support releasing the genetically-engineered mice into the wild, it would theoretically break the transmission cycle of the disease further down the food chain from the deer. As was noted above, several other reservoir species such as shrews, rats, robins (Turdus migratorius), and chipmunks (on Martha's Vineyard), might continue to infect ticks (table 2). The book includes interviews with Willy Burgdorfer, who is credited with discovering the bacteria that causes Lyme disease. Allison Snow (snow.1@osu.edu) 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. Dead white-footed mice also provide carrion for scavengers, including several species of burying beetle (Nicrophorus spp., McKenna-Foster et al. Specific plans for how the first field releases will be carried out and evaluated have not been finalized, and several strategies are being considered. These types of hypothetical scenarios and others may be unlikely, but it is useful to employ a problem formulation approach to identify which outcomes are deemed possible by knowledgeable experts. White-footed mice hoard and consume acorns, and can benefit tree species by preying on gypsy moth pupae (Lymantria dispar, Jones et al. Infected ticks rarely transmit Lyme spirochetes to their offspring, which must feed on a reservoir host to become infected (e.g., Piesman et al. In addition to effects associated with engineered resistance traits per se, insertions of the resistance cassette might have unanticipated pleiotropic effects on mouse phenotypes, especially if individual mice have multiple copies of the cassette. Because Lyme disease was discovered relatively recently, there are some who believe Lyme is either a man-made disease or a genetically engineered version of an older form. Noting that the University of Maryland has pioneered the science and practice of creating transgenic fungi, St Leger said that he and colleagues at Maryland and at partnering institutions are already working to create genetically engineered fungi that can be used to reduce transmission of other illnesses, like Lyme disease and sleeping sickness. With 300,000 people in the United States falling ill with Lyme disease every year, according to the Centers for Disease Control, chances are there are others who, like Forando, are unaware a vaccine ever hit pharmaceutical shelves. Several research questions posed in the present article would be highly suitable for graduate students’ theses and dissertations, whereas others are more feasible for the MIT–Tufts group, other research teams, or professionals who work with citizen-science collaborators. In addition, these mice prey on the eggs of ground-nesting songbirds (e.g., veeries, Catharus fuscescens, Schmidt et al. Possible environmental risks of releasing genetically engineered (GE) vertebrates into natural habitats (adapted from Snow et al. 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). One possible solution was to reduce their numbers, but that was unpopular with residents, Lepore said. This project is one of many that aim to use genetic editing tools to modify animals’ DNA to stop diseases like Lyme, malaria and schistosomiasis. According to reported cases of Lyme Disease (1992-2004), those most affected were boys aged between 5 and 9. 2006). Like many wildlife species, white-footed mice are viewed as a pest when they cause damage in and around human habitation or serve as a vector for human diseases. Plum Island comes under the control of DHS: “On November 21, 2002, President Bush signed legislation creating the Department of Homeland Security (DHS) to unify Federal forces and protect our Nation from a new host of terrorist threats. Nichols averred that there was frequent collaboration between the two facilities. Can a transgenic chestnut restore a forest icon? Little interplot movement would be expected because white-footed mice have a relatively small home range (Wolff 1985, Tsao et al. Schematic of ecological interactions that influence the prevalence of Lyme-infected ticks in the northeastern United States. Lyme disease is caused by the bacterium Borrelia burgdorferi. Lyme disease is an infectious disease caused by the Borrelia burgdorferi bacterium. 2006, Levi et al. Meanwhile, gene drive research to eradicate mosquito populations that carry malaria is already well underway (Kyrou et al. Tick-borne disease has been rising over the past few decades and mice are seen as the main reservoir for the bacteria that cause Lyme and other diseases. Nonetheless, large-scale field experiments in Connecticut and New York showed that the vaccinating white-footed mice against Lyme decreased the local frequency of Lyme-infected nymphs (Tsao et al. 2019). In addition, Massachusetts Division of Fisheries and Wildlife may require that the genetic uniqueness of island populations on Nantucket and Martha's Vineyard be preserved (personal communication, Thomas French, Massachusetts Division of Fisheries and Wildlife, 18 February 2019). 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. Thread starter lymegreen; Start date Jun 9, 2016; Status Not open for further replies. Smith RP, Rand PW, Lacombe EH, Telford SRIII, Rich SM, Piesman J, Spielman A. Esvelt KM, Smidler AL, Catteruccia F, Church GM. We must also hope that some doctors do the same, as there have been many reports of sufferers being wrongly diagnosed and treated badly when they have requested further investigation. ... the bacterium that causes Lyme disease. 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. Although human studies on the health effects of genetically modified organisms (GMO), also referred to as GM foods, are lacking at present, the LIA believes they should be avoided until proven safe, especially the most vulnerable such as those suffering autism, Lyme disease, and other chronic illnesses. Nichols told Quinn that the disease was first engineered in the mid-1960s and was initially released at the Montauk base itself and the surrounding communities. LoGiudice K, Ostfeld RS, Schmidt KA, Keesing F. Markowski D, Ginsberg HS, Hyland KE, Hu R. Mckenna-Foster A, Perrotti L, Blyth J, LoPresti E, Kennedy RS. At my request, James led me down to the insectary where his lab at U.C. 1993); Norway rat, Rattus norvegicus (Monhegan, Maine; Smith et al. However, differentiation among the island and mainland populations may be relatively small given the large amount of genetic, morphological, and behavioral variation found in this species across its range (Bedford and Hoekstra 2015). Do GE mice differ from non-GE mice in outdoor mesocosm experiments that are designed to evaluate fitness-related traits, such as survival, growth, behavior, and reproduction? 2015, NASEM, 2016, Harvey-Samuel et al. In a similar vein, as is described in the present article, GE Lyme-resistant white-footed mice (Peromyscus leucopus) are being developed to combat Lyme disease by proliferating freely on the islands of Nantucket and Martha's Vineyard, Massachusetts. Although Lyme Disease can (and does) exist worldwide, it was "discovered" in 1975 near Lyme, Connecticut, hence the name. Request PDF | On Dec 2, 2019, Pedro Ducos and others published Graphene transistor arrays functionalized with genetically engineered antibody fragments for Lyme disease diagnosis | … Despite considerable publicity, this project has yet to be evaluated by independent professional ecologists. Pages 18–47 in EDITORS, eds. 1990, Brisson et al. ” and learn how impact inventing might help … At the state level, the Massachusetts Division of Fisheries and Wildlife regulates the release of all wildlife species regardless of their GE status (www.mass.gov). 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. The Centers for Disease Control and Prevention estimates the number of cases at about 300,000 per year.1 Lyme disease, which causes fever, fatigue and headaches, can usually be successfully treated with … Most human infections are acquired from nymphs (Piesman et al. Culling deer to reduce their role as hosts for adult ticks is often mentioned as part of an integrated management plan for reducing Lyme and other tick-vectored diseases, but this approach is controversial (e.g., Kugeler et al. They also called for a moratorium on all GM foods and for "Research to evaluate the role of GM foods on autism, Lyme disease, and related conditions." Also, several of the team's grant proposals and community presentations are available online at www.responsivescience.org/mice-against-ticks. 2017). Going forward, interdisciplinary cooperation and proactive risk assessment research will be needed to identify appropriate uses of genome editing in wild vertebrates and to avoid unwanted outcomes. 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. 1) Lyme disease is endemic to all land areas surrounding Plum Island. Doxycycline is the drug of choice for both diseases. If field trials on small, experimental islands are successful, the project would scale up to the larger islands of Nantucket and Martha's Vineyard, Massachusetts, and possibly to the mainland, most likely with a local gene drive to speed the traits’ proliferation, pending approvals from relevant constituents. According to res… The need for careful environmental risk assessment has been widely acknowledged (e.g., Webber et al. More than 22 Federal agencies were consolidated into the new department, including portions of the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS)…..on June 1, 2003, the property and facilities of USDA’s Plum Island Animal Disease Center, jointly run by APHIS and USDA’s Agricultural Research Service (ARS), are being transferred to DHS.”. Although the Mice Against Ticks project is still at an early stage of development, Esvelt's team has publicized their intial methods and long-term goals well in advance to encourage early involvement and oversight from various stakeholders (Buchthal et al. According to the USDA “There are no secrets at Plum Island,” but are they really telling us everything? On the basis of my informal inquiries, federal agencies appear to be waiting for a concrete application to be submitted before they are able to identify which regulations and procedures would apply. 2003), but masked shrews (Sorex cinereus), short-tailed shrews (Blarina brevicauda), and chipmunks (Tamias striatus) also can function as reservoir species (table 2; Telford et al. Moreover, possible founder effects or several generations of rearing mice in captivity might result in a loss of traits that enhance their survival in the wild, including, for example, the ability to survive cold winters or years with very low acorn production. If the experiment drastically reduces the amount of tick borne disease on the island, Esvelt said he believes the genetically engineered mice could eventually be used on the mainland. 2019). Graphene transistor arrays functionalized with genetically engineered antibody fragments for Lyme disease diagnosis To cite this article: Zhaoli Gao et al 2020 2D Mater. For example, in a New York forest, Brisson and colleagues (2008) estimated that shrews fed 55% of infected ticks, whereas white-footed mice fed only 25%. The idea is that when the genetically engineered mice mate with the native mice, their offspring would also be immune to Lyme disease. 2016). Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by the Borrelia bacterium which is spread by ticks. An examination of museum specimens ofIxodes ticks showed that the presence of Lyme disease spirochetes in suitable arthropod vectors preceded — by at least a generation — the year (1982) when Lyme disease was first recognized as a distinct clinical entity in the U.S. (1, 2). Noting that the University of Maryland has pioneered the science and practice of creating transgenic fungi, St Leger said that he and colleagues at Maryland and at partnering institutions are already working to create genetically engineered fungi that can be used to reduce transmission of other illnesses, like Lyme disease and sleeping sickness. Despite outreach and media attention, only half of the community was aware of the proposal; half of those were supportive. The following extract was taken from a USDA site regarding the facility on Plum Island: “Today, biotechnology has advanced to the point where such work could safely be done in a facility on the mainland, but the island setting offers the U.S. livestock industry an extra measure of protection. Esvelt first asked residents if they even wanted white-footed mice that were genetically engineered to fight tick-borne disease and, if so, what exactly the mice should be resistant to — Lyme disease or ticks in general. Residents said they’d ideally want the white-footed mice to be resistant to both Lyme disease and ticks. The best-selling book Bitten: The Secret History of Lyme Disease and Biological Weapons that was published in May of this year, exposed the potential for ticks to be weaponized and spread Lyme disease. Published by Oxford University Press on behalf of the American Institute of Biological Sciences, This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, Ready, Set, Go: Community Science Field Campaign Reveals Habitat Preferences of Nonnative Asian Earthworms in an Urban Landscape, Decline of Amateur Lepidoptera Collectors Threatens the Future of Specimen-Based Research, A Clarion Call for Informed Decision-Making. Kugeler KJ, Jordan RA, Schulze TL, Griffith KS, Mead PS. One possibility is to use replicated experimental plots (approximately 0.4 hectares) that are more than 500 meters (m) away from each other on same island, with two types of introductions, GE versus non-GE white-footed mice. Anthropologist Barbara J. The bacteria was isolated and identified in 1981 by Willy Burgdorfer. 2004, Brisson et al. 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. As was noted by Hayes and colleagues (2014), this very challenging task is initiated by asking many hypothetical what-if questions. Clearly, as the Mice Against Ticks project moves forward, future workshops, focus groups, and peer-reviewed publications that examine and evaluate possible environmental hazards are warranted, including studies that are carried out by independent researchers. APHIS regulates certain GE organisms that may pose a risk to plant or animal health. 2017). Kyrou K, Hammond AM, Galizi R, Kranjc N, Burt A, Beaghton AK, Nolan T, Crisanti A. Levi T, Kilpatrick AM, Mangel M, Wilmers CC. 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. The current plan is to iteratively outcross GE white-footed mice with local island populations. 2019). Findings from the first field releases on small islands will be reported in peer-reviewed publications for the benefit of various stakeholders, scientists, funding agencies, and regulatory agencies. Search for other works by this author on: Box 1. To what extent do frequencies of Lyme-infected ticks decrease over time as was expected? After a dengue outbreak in Key West, Florida, during 2009–2010, authorities, considered conducting the first US release of male Aedes aegypti mosquitoes genetically modified to prevent reproduction. How will genome-edited white-footed mice be regulated? But sadly this seems an exception to the rule. 7 024001 View the article online for updates and enhancements. 2005). One can imagine many reasons why introductions of GE white-footed mice might not have the intended outcomes of reducing Lyme infections in blacklegged ticks. 2010). Fitness compared to infected, non-GE mice with Lyme resistance this field is so new, Piesman J Liu! Patience Island, Rhode Island ; Markowski et al, Schmidt KA, Schauber,... Species diversity honest stories that engage readers, Lunshof J, Liu J, Spielman a July attract highest. 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