Lyme disease is a serious menace to human and animal health. Caused by bacteria in the genus Borrelia, this disease follows a pattern reminiscent of syphilis in which unresolved infections may disseminate to create a broad spectrum of debilitating chronic damage. A mysterious cluster of arthritis cases appearing near the town of Old Lyme, Connecticut, led to the recognition of what is now known as Lyme disease (1).
Lyme disease is spread by tick bites and is currently the most common tick-borne infection in the U. S. and other locations. The Centers for Disease Control and Prevention (CDC) estimates that over 300,000 cases of Lyme disease occur annually in the U. S. (2), predominately in restricted geographic areas. Ticks acquire and spread the disease by feeding on wild animals such as white-footed mice (Peromyscus leucopus) which harbor the bacteria. Dogs and cats may get Lyme disease and while they do not spread it to their owners directly, they may bring infected ticks into the home.
Although Lyme disease may (in principle) be controlled in several ways, it continues to pose a significant health threat. This persistence coupled with its serious consequences has led to several proposals to suppress infections. The most recent is a strategy proposed for Nantucket Island to genetically engineer white-footed mice to resist becoming infected with tick-borne disease-causing bacteria (3). These mice are a key reservoir for the Lyme disease-causing Borrelia burgdorferi bacteria and making them resistant could break the chain of transmission to humans and other animals. Nantucket Island has been impacted heavily by Lyme disease and seems to be an ideal place to test this idea. Scientists promoting this study have initiated proactive public outreach efforts to explain, discuss and build support for this research (3).
If all goes according to plan white-footed mice that produce antibodies making them resistant to infection with Borrelia burgdorferi will be constructed and tested in the laboratory. The genetically engineered mice will be mass produced and put on an uninhabited island nearby to see if their presence results in fewer B. burgdorferi-infected ticks. If that works, hundreds of thousands of engineered mice will be released on Nantucket. The effort will require years to execute and fully assess as well as major financial resources. The idea looks promising, but there are no guarantees of success at any stage nor is it clear whether it will be feasible to use this approach in other areas hit hard by Lyme disease.
Work of this nature will require governmental agency approvals and selling it to the public may be challenging. Lyme disease is treatable with antibiotics or avoidable through several active measures to repel or avoid ticks (4) and a new human vaccine will undergo safety testing soon (5). In addition, would-be genetic engineers face several directly competing technologies (6) some of which have successfully completed long-term field trials (7). Nantucket citizens, understandably anxious to take immediate action to curtail Lyme disease in their vicinity, may prefer to try the already developed mouse vaccine alternatives rather than undertaking a long duration genetic engineering research program. However, the ecology of Lyme disease is complex and both mouse vaccination and genetic engineering strategies target only one of the bacterial reservoirs. A new species of Lyme disease bacterium, Borrelia mayonii, has been discovered (8), suggesting assumptions regarding transmission may need to be revised. Despite the fact that several effective control measures exist, treating or preventing Lyme disease has been frustrating. History admonishes us there may be no simple, single means to achieve this goal.
Every project will have some weaknesses and multiple scientific objections to controlling Lyme disease by genetic engineering of mice have been raised (3). However, this complicated situation has another wrinkle – the proposed Nantucket effort will be useful almost nowhere else. If successful it will serve as an indirect proof-of-concept for an overarching plan to justify using gene drives for disease abatement (9). Instead of having to construct and rear enormous numbers of engineered mice in the lab, gene drives placed in a few animals released in the wild would spread through the population on their own. The compelling idea is gene drives could more conveniently render wild white-footed mice resistant to B. burgdorferi and break the chain of transmission of Lyme disease. However, the efficacy and full risks of this approach might be hard to judge over short time spans and gene drives could permanently alter the environment in ways that may not be reversible.
The questions proposed for study on Nantucket Island are scientifically interesting with highly significant implications for human and animal health. The proposal to create and release genetically engineered mice to control Lyme disease is still in the formative stages and it will be interesting to see what comes forth. If the prime objective is to simply demonstrate the mouse-human chain of Lyme disease transmission can be broken to justify future gene drive experiments, proponents will do well to note some of that work has been accomplished. Vaccinating wild animal populations using oral baiting broadcast methods has stopped the spread of rabies viruses (10) and field-tested mouse vaccines to control Lyme disease (7) are ready to deploy. If the mouse vaccines reduce human infections, mass scale field tests of genetically engineered mice on Nantucket completed several years later may not yield much additional benefit relative to the time, expense and effort invested. At this stage testing the mouse vaccine strategy warrants being given a high priority as well as proper due consideration by anyone proposing to solve the Lyme disease problem.
In the final analysis, gene drives will be forced to compete with other Lyme disease control methods and will ultimately be judged on their efficacy, safety, environmental impact and economic feasibility. In addition, public acceptance will be a factor as some persons, even in localities facing the prospect of threatening disease outbreaks, have deep concerns about environmental management through genetic manipulation (11). That plus concerns expressed by scientific colleagues regarding motivations (3) should alert project proponents with vested interests to ensure their proposed research unequivocally and directly serves the public interest. To some scientists gene drive technology is the coolest thing around and they are seeking a situation to use it. The CRISPR-based gene drive is a remarkable concept and perhaps research will actually reveal it provides the best means to combat Lyme disease. The real goal is defeating Lyme disease as quickly as possible.
(1) S. Elbaum-Garfinkle. 2011. Close to Home: A History of Yale and Lyme Disease. Yale Journal of Biology and Medicine 84:103-108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117402/
(2) U. S. Centers for Disease Control and Prevention. https://www.cdc.gov/lyme/stats/humancases.html
(3) B. J. King. 2016. Are Genetically Engineered Mice the Answer to Combating Lyme Disease? National Public Radio (NPR), 16 June 2016. http://www.npr.org/sections/13.7/2016/06/16/482279851/are-genetically-engineered-mice-the-answer-to-combating-lyme-disease
(4) U. S. Centers for Disease Control and Prevention. https://www.cdc.gov/lyme/prev/index.html
(5) D. Mosher. 2016. A New Lyme Disease Vaccine Will Soon be Tested on Americans and Europeans. Business Insider, 9 December 2016. http://www.businessinsider.com/lyme-disease-vaccine-valneva-clinical-trial-2016-12
(6) W. Moyer. 2015. The Growing Global Battle Against Blood-sucking Ticks. Nature, 25 August 2015. http://www.nature.com/news/the-growing-global-battle-against-blood-sucking-ticks-1.18227
(7) L. M. Richer et al. 2014. Reservoir Targeted Vaccine Against Borrelia burgdoferi: A New Strategy to Prevent Lyme Disease Transmission. The Journal of Infectious Diseases 209:1972-1980. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038139/
(8) U. S. Centers for Disease Control and Prevention. https://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html
(9) A. Harmon. 2016. Fighting Lyme Disease in the Genes of Nantucket’s Mice. The New York Times, 7 June 2016. http://www.nytimes.com/2016/06/08/science/ticks-lyme-disease-mice-nantucket.html
(10) J. L. Elser et al. 2016. The Economics of a Successful Raccoon Rabies Elimination program on Long Island, New York. PLoS Neglected Tropical Diseases, 9 December 2016. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005062
(11) L. Alvarez. 2016. In Florida Keys, Some Worry About ‘Science and Government’ More Than Zika. The New York Times, 24 August 2016. http://nyti.ms/2bFFsL2
Note to readers – I have no competing financial or scientific interests in any Lyme disease control research or products.