Irvine breeds genetically engineered mosquitoes to study, for example, whether they can be made malaria-resistant. 2014, Buchthal et al. 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). 2017). Graphene transistor arrays functionalized with genetically engineered antibody fragments for Lyme disease diagnosis To cite this article: Zhaoli Gao et al 2020 2D Mater. Bensaci M, Bhattacharya D, Clark R, Hu LT. Brossard D, Belluck P, Gould F, Wirz CD. 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. 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. According to researchers, it’s the biggest carrier of Lyme disease on the island making it a prime opportunity for experimenting with new techniques to reduce transmission to humans. 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. The idea is that when the genetically engineered mice mate with the native mice, their offspring would also be immune to Lyme disease. Meanwhile, gene drive research to eradicate mosquito populations that carry malaria is already well underway (Kyrou et al. According to the USDA “There are no secrets at Plum Island,” but are they really telling us everything? University of Michigan Museum of Zoology Publication no. 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. Experimental releases could be carried out over a period of several years to increase frequencies of GE mice as needed. Possible environmental risks of releasing genetically engineered (GE) vertebrates into natural habitats (adapted from Snow et al. This project is designed to be a first step toward larger scale introductions on the mainland and does not involve a gene drive (Buchthal et al. 1) Lyme disease is endemic to all land areas surrounding Plum Island. Under FDA’s draft guidance for industry no.187, revised in January 2017, the agency regulates “intentionally altered genomic DNA in animals,” including the use of CRISPR, under the process for evaluating “new animal drugs” (e.g., www.fda.gov). 45, Reducing resistance allele formation in CRISPR gene drive, Genetic diversity and conservation units: Dealing with the species-population continuum in the age of genomics, Assessing ecological and evolutionary consequences of growth-accelerated genetically engineered fishes, Invasion and migration of spatially self-limited gene drives: A comparative analysis, Reservoir competence of white-footed mice for Lyme disease spirochetes, The American Journal of Tropical Medicine and Hygiene, The new frontier of genome engineering with CRISPR-Cas9, Tick-borne zoonoses in the United States: Persistent and emerging threats to human health, Genome sequencing and population genomics in non-model organisms, Concerning RNA-guided gene drives for the alteration of wild populations, Modeling the role of songbirds and rodents in the ecology of Lyme disease, A regional study of diversity and abundance of small mammals in Ohio, Towards the genetic control of invasive species, Meeting the challenge of quantitative risk assessment for genetic control techniques: A framework and some methods applied to the common Carp (. 3) Lyme Disease and Gulf War Illness share almost identical symptoms. 2019). Reprinted with permission from Levi and colleagues (2016). Lyme Disease Support Group. 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. 2019). Is this not creating an additional target for attack and increasing the risk to the US population? As was noted by Hayes and colleagues (2014), this very challenging task is initiated by asking many hypothetical what-if questions. To promote the success of introduced mice, local mice may be trapped and removed prior to these experimental releases, whereas introduced mice could be provided with nest boxes. 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. One risk assessment concern that is relatively straightforward to address empirically pertains to population-genetic effects of releasing massive numbers of GE white-footed mice that have been reared in controlled, laboratory environments. Kugeler KJ, Jordan RA, Schulze TL, Griffith KS, Mead PS. 2018). “Lyme disease is our natural disaster.” More than 300,000 people in the United States are diagnosed with it each year. 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. There is a very strong connection between the current growth of Lyme Disease infections and the research center on Plum Island. CRISPR-based genome editing will be used to insert the resistance cassette into white-footed mouse lines, possibly with multiple copies of the resistance cassette in each mouse. 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. [NASEM] National Academies of Sciences, Engineering, and Medicine. For example, using older techniques, the once-common American chestnut (Castanea americana) has been genetically engineered to resist the chestnut blight fungus that nearly drove this species to extinction (Popkin 2018). 2018a). Other unwanted disruption of biotic communities, including disruption of ecosystem services. There is one of only two possible realities that could have unfolded in regards to Lyme disease "originating" on Plum Island, New York. Saved by JoAnn Hoffman Logan. However, some appear to have a better immune system than others (especially those of certain ages) and are able to rid themselves of the disease with little or no treatment. 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 … Examples of host species, reservoir competence, and presence on Nantucket and Martha's Vineyard, including two bird species that forage on the ground. On Martha's Vineyard and in Nantucket, Kevin Esvelt, an evolutionary biologist at MIT, has proposed fighting Lyme disease using genetically engineered mice. Nantucket could become the site of an unprecedented experiment to combat Lyme disease by releasing genetically modified mice on the island. Because the earliest, small-scale field trials with GE white-footed mice are not likely to take place in the next 3–5 years, at the earliest, or more likely several years later because of engineering difficulty, coordinated research can be initiated soon to address key questions related to risk assessment. At my request, James led me down to the insectary where his lab at U.C. Given the importance of wildlife and natural areas to many of the islands’ residents and visitors, as well as the compelling need to reduce Lyme disease, this proposal to introduce GE Lyme-resistant white-footed mice will be of great interest to local residents and organizations such as the Massachusetts Audubon Society, the Nantucket Biodiversity Initiative, and, on Martha's Vineyard, the Wampanoag Tribe of Gay Head (Aquinnah) and BiodiversityWorks (https://biodiversityworksmv.org). 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. Another question is whether constitutive production of resistance antibodies by GE mice could impose an underlying fitness cost, with or without spirochete infection. For example, one could ask whether planned, massive introductions of GE white-footed mice with Lyme resistance conceivably could lead to the unwanted outcomes shown in table 1. Genetic engineering of wild populations has been proposed for reducing human diseases by altering pathogens’ hosts. A Drug Maker Halo For a Covid Vaccine? Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? Nonetheless, public engagement about potential benefits and risks is incomplete without considering existing ecological expertise and knowledge relevant to each proposed application (NASEM 2016). The numbers fall a little for those aged around 20-29, but rise again after the age of 30, peaking at an age group of 60-69. 1993); Norway rat, Rattus norvegicus (Monhegan, Maine; Smith et al. Although human studies on the health effects of genetically modified organisms (GMO), also referred to as GM foods, are lacking at present, … 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. Also, several of the team's grant proposals and community presentations are available online at www.responsivescience.org/mice-against-ticks. In formal environmental risk assessments for regulatory decision-making, researchers attempt to identify specific, measurable hazards and the likelihood of such hazards (e.g., Hayes et al. 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. ” and learn how impact inventing might help … 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). 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. Huang C-I, Kay SC, Davis S, Tufts DM, Gaffett K, Tefft B, Diuk-Wasser MA. Dhole S, Vella MR, Lloyd AL, Gould F. Eisen RJ, Kugeler KJ, Eisen L, Beard CB, Paddock CD. Noncompliance with legal or regulatory requirements, or with ethical standards for research and deployment of GE animals. Shrews are more difficult to census accurately than white-footed mice, and standard live-trapping methods underestimate their abundance (Harder et al. Anthropologist Barbara J. 1991). Novel public health strategies require community … The white footed mouse is another common tick target. What is the ecological role of white-footed mice as predators, competitors, and prey? It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. One possible solution was to reduce their numbers, but that was unpopular with residents, Lepore said. 2016). As is widely acknowledged with previous types of transgenic organisms, each proposed use of genome editing in wild species should be assessed on a case-by-case basis to examine why, how, when, and where these techniques would be used (e.g., Snow et al. Lyme disease is an infectious disease caused by the Borrelia burgdorferi bacterium. Copper marks strong price performance in 2020, what is driving the trend? President George Bush has publicly admitted that accidents have occurred on the island, which makes the decision to move to the mainland somewhat risky. 2017, Piaggio et al. Another consideration is whether the island populations of white-footed mice are distinct enough to merit special conservation status. 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. 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. Prior to any releases on Nantucket or Martha's Vineyard, smaller nearby, privately owned islands will be used in field trials (Buchthal et al. Some believe that the spread of this terrible disease was either as a … White-footed mice typically survive for less than 1 year; females have about two litters per year, with three or four pups per litter (Spielman et al. The book includes interviews with Willy Burgdorfer, who is credited with discovering the bacteria that causes Lyme disease. 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. GMOs: pervasive and high-risk. 2005), with examples of hypothetical, worst-case scenarios for the current case study involving GE Lyme-resistant white-footed mice. 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. Spielman A, Etkind P, Piesman J, Ruebush TKII, Juranek DD, Jacobs MS. Tsao JI, Wootton JT, Bunikis J, Luna MG, Fish D, Barbour AG. Nearly 40 percent of the residents of Nantucket Island in Massachusetts have had Lyme disease. The project would still be years down the road. Doxycycline is the drug of choice for both diseases. Ticks require a single blood meal during each stage of their 2-year life cycle, as larvae, nymphs, and adults (females only); larvae and nymphs feed primarily on small mammals, whereas female adults feed primarily on deer (Figure 2; e.g., Anderson 1988, but see Huang et al. “We’re making mice that are 100 percent white-footed mice, but can’t be reservoirs for tick-borne diseases,” Esvelt said. There is some speculation that large amounts of these insects escaped with “biologically engineered/altered strains” of Lyme disease that is now matching those seen in the newer cases in the US. February 7, 2017. Ticks live in shrubs and underbrush, waiting for an unsuspecting animal to come by that they can latch on to. 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). As scientists battle bitter backlash over a plan to release genetically modified, Zika-killing mosquitoes in the Florida Keys, just 1,700 miles north a similar plan has caused much less of a fuss. 1987, Lane et al. I can not confirm the accuracy of this information. Most of these claims center around the Plum Island Animal Disease Center in New York, and many of them come from the website of bullshitter extraordinaire Jeff Rense. The resulting mice will be engineered to be immune (to either Lyme or tick bites or both), but will be 100 percent mouse with respect to their DNA. 2017, 2017), but realistic case studies involving free-living GE vertebrates are scant, in part because this field is so new. Does the introduction of GE white-footed mice alter the transmission dynamics of other tick-borne pathogens? 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. 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). Results from research in New England, including studies of several island communities, show that both the presence of deer and the presence of an abundant, small-mammal reservoir species are typically required for blacklegged ticks to persist and cause outbreaks of Lyme disease (e.g., Telford 2017 and references therein). Specifically, the Code of Massachusetts Regulations (321 CMR 2.15[4]) states that a permit is required to release wild animals on the basis of stipulations of the state's wildlife management practices. The program involved genetically modified ticks and the researchers wanted to see the potential for biological weapons through Lyme disease. 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. If results from small-island introductions of GE mice yield promising results, scaling up to releases on Nantucket or Martha's Vineyard would be considered, pending approvals from regulatory agencies and local representatives or town meetings. There was once a Lyme disease vaccine sold in the US, yanked off the market only after a few years. Spatial heterogeneity in predator activity, nest survivorship, and nest-site selection in two forest thrushes, Norway rats as reservoir hosts for Lyme disease spirochetes on Monhegan Island, Maine, Genetically engineered organisms and the environment: Current status and recommendations, Reservoir hosts of human babesiosis on Nantucket Island, American Journal of Tropical Medicine and Hygiene, An ecological approach to preventing human infection: Vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle, Deer reduction is a cornerstone of integrated deer tick management, Short-tailed shrews as reservoirs fo the agents of Lyme disease and human babesiosis, Linking behavior, life history, and food supply with the population dynamics of white-footed mice, The Lyme disease pathogen has no effect on the survival of its rodent host, The systematic position of white-footed mice, genus. Characteristics of GE white-footed mice compared to local populations. 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. 2005), with examples of hypothetical, worst-case scenarios for the current case study involving GE Lyme-resistant white-footed mice. Any of … Thus, the name of the disease emerged. Anthropologist Barbara J. Scientists at MIT are hoping to prevent Lyme disease on the Vineyard by releasing large numbers of genetically engineered mice into the wild. 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). 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. Alternatively, the research team may attempt to inundate an entire small island with GE mice, possibly in tandem with studies at an unaltered control island with no intervention and a non-GE control island with lab-reared white-footed mice that lack the GE cassette. Lyme disease is caused by the bacterium Borrelia burgdorferi. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. 2008). I was shocked to read this statistic in The New York Times As some may be aware, the research center at Plum Island is shortly going to be moved to the mainland, much to people’s horror. 2019). Toward this goal, academic researchers are developing Lyme-resistant and tick-resistant white-footed mice, which are a primary pathogen reservoir for Lyme disease in the United States. 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. 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. Copyright © 2021 American Institute of Biological Sciences. 2018). 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. On Nantucket and Martha's Vineyard, which lack many mainland mammal species (supplemental table 1), white-footed mice are the most common reservoir species captured in live traps (Spielman et al. Buchthal J, Evans SW, Lunshof J, Telford SRIII, Esvelt KM. Picture many thousands of mice let loose on a Massachusetts island in an effort to fight Lyme disease. 2017). 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). Doxycycline is the drug of choice for both diseases. 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. If this occurs, do positive feedback loops also reduce Lyme infection levels in other reservoir species, such as masked shrews, short-tailed shrews, or chipmunks? 2017). 2019). Loss of genetic diversity within species. 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. ... the bacterium that causes Lyme disease. 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.”. (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). 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%. 2005, NASEM 2016). All News. 2014). 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. 2006). But what of Plum Island? 2016). However, it should be noted that many doctors have failed to discover this disease in some patients (for various reasons), so the actual figures are almost certainly much higher! 1) Lyme disease is endemic to all land areas surrounding Plum Island. The months of June and July attract the highest number of reported cases. In this region, it appears that the majority of infected larvae and nymphs may feed on reservoir host species other than white-footed mice (LoGiudice et al. 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). The white-footed mouse is often considered to be one of the most effective and abundant reservoir species for Lyme spirochetes in the northeastern United States (Piesman and Spielman 1979, Donahue et al. According to the Massachusetts Department of Public Health, almost 9,000 cases of Lyme disease have been reported across the state between 2015 and 2016. As with most diseases, if you catch it in the early stages, there is a greater chance of a cure. 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). 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. Lyme disease is an infectious disease caused by the Borrelia burgdorferi bacterium. Are local populations of white-footed mice distinct subspecies compared to populations on other islands and the mainland? Experiments carried out under seminatural conditions will be helpful for identifying possible fitness differences between GE and non-GE mice, although the full range of such outcomes may not be evident in small-scale, short-term studies. The first is that Lyme disease originated on Plum Island, and by "originated" we could only mean "a genetically modified single celled organism" and not born or created. 3) Lyme Disease … Lyme Disease is not unique to the United States, it appears all over the world. 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. 7 024001 View the article online for updates and enhancements. 2015, NASEM 2017, Dhole et al. As Lyme disease casts a shadow over New Englanders’ outdoor expeditions, MIT researchers have proposed using gene editing to fight the disease. 2017). If the native mouse lines used for rearing the GE lineages already include high levels of genetic diversity, severe bottlenecks and genetic drift can be minimized, depending on methods used for creating and maintaining these lineages. Lyme disease diagnosis is currently held back by a lack of reliable Many previous publications describe environmental risk assessment questions that arise whenever a new type of genetically engineered organism is developed for agriculture, forestry, aquaculture, or other applications (e.g., NAS 2002, Snow et al. Effects of introducing GE white-footed mice with Lyme resistance. 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. 2015), logistically challenging, and may not be effective unless deer densities can be maintained at fewer than approximately 5 deer per square kilometer (Telford 2017). 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. 1986). This process represents the first phase of “problem formulation” used by regulatory agencies to evaluate GE organisms (e.g., Wolt et al. However, the research team expects that established populations of Lyme-resistant white-footed mice would deplete a major reservoir source for transmission of the spirochete, thereby significantly decreasing the proportion of Lyme-infected blacklegged ticks over time, and perhaps initiating a self-reinforcing feedback loop (personal communication, Kevin Esvelt, Massachusetts Institute of Technology, March 8, 2019, and Sam Telford III, Tufts University, March 7, 2019). The white footed mouse is another common tick target. 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Have proposed using gene editing to fight the disease human diseases by altering pathogens ’.!, those most affected were boys aged between 5 and 9 have altered fitness compared to infected, non-GE.!