An Interview with Robert S. Lane,Ph.D.

VBZD: Dr. Lane, you originally studied psychology but then switched to entomology. This seems like an unusual change of direction. What led to this switch and are you pleased that you chose to pursue a career in entomology?

RSL: I enjoyed majoring in psychology at the University of California, Berkeley (UCB), but I realized that there were not many job opportunities for someone with a Bachelor's degree in that field. Another reason for the switch was my long-term interest in science in general and field biology in particular. At the age of 8, I began collecting insects, arachnids, and reptiles in Los Angeles. At that time there were vast open spaces in parts of the city, such as the Baldwin Hills area, where a nascent entomologist could roam for hours looking for insects, trap-door spiders, scorpions, lizards, and snakes.

After I graduated from UCB, I went to San Francisco State College and completed a second undergraduate major and a Master's degree, both in biology. I had taken a course in general entomology that piqued my interest in insects again, and I decided that I wanted to become an entomologist. A subsequent course in medical entomology led to my decision to pursue that subdiscipline as a specialty. I applied for and was accepted to the Ph.D. program in entomology at UCB. I never expected to end up on the faculty of the university where I completed my Bachelor's and Ph.D. degrees, but that is what happened 10 years after I completed my formal education.

VBZD: How did you decide to become a tick biologist?

RSL: My first job was as a public health biologist at the California State Department of Health Services (CSDHS), where I spent 5 years working as a member of the Vector Biology and Control Section. My duties included investigating diverse aspects of vector ecology and management in the San Francisco Bay region. One of the research projects I was encouraged to pursue was determining the identity of the tick vector of Rocky Mountain spotted fever (RMSF) in western California. Although I had never worked on ticks before—my Ph.D. dissertation topic had been the biology and taxonomy of horse flies and deer flies (Tabanidae)—I eagerly switched over to tick research and, in 1974, I began a 5-year collaborative study to elucidate the tick vectors and vertebrate hosts of spotted fever–group rickettsiae. That work also led to ancillary investigations of the potential tick vectors and hosts of Colorado tick fever virus and the agent of tularemia. Within a few years, I became the statewide consultant on ticks and tick-borne diseases. In 1980, I relinquished my position at the health department and returned to my alma mater as a research specialist in medical/veterinary entomology. I continued my tick studies at UCB until a faculty position in medical entomology opened up there, which I was offered in 1984. Since then, the primary focus of my research program has involved studying the biology of ticks and the ecology, epidemiology, and prevention of tick-borne disease agents, especially Lyme disease spirochetes.

VBZD: The number of universities offering training in classical entomology has declined over the years, entomology departments have closed, and, at present, entomology often focuses on molecular techniques. What has been the impact of this reduced opportunity for training, and especially field training, given that the incidence of tick-borne pathogens has not declined and that many of the pathogens transmitted by ticks are classified as high priority for research since they are regarded as potential agents for bioterrorism?

RSL: In view of the public health significance of ticks in the United States, there is a puzzling lack of young scientists being trained in tick field research. Approximately 90% or more of all human cases of vector-borne diseases presently reported to the Centers for Disease Control and Prevention (CDC) are transmitted by ticks. For that reason, one might expect that there would be more academic programs training graduate students in the study of tick-borne diseases. Looking back over my career, I also have noticed that many of the same field researchers who were presenting papers on Lyme disease at national or international scientific meetings 20 to 25 years ago have remained active to the present, but the number of younger investigators participating is less than I anticipated it should be.

I am uncertain why this is the case. Admittedly, there have been some funding opportunities through the CDC, such as its Lyme Disease Cooperative Agreement program, and through the National Institutes of Health (NIH), such as its RO1 grants program. Nevertheless, one of the major impediments appears to be a dearth of training programs that target tick research. An excellent paradigm for such training was the international course on the Biology of Disease Vectors that began in 1990 and ended a few years ago. The Wellcome Trust, John D. and Catherine T. MacArthur Foundation, and the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases sponsored the course. It trained hundreds of students, postdocs, and faculty and promoted basic research on vectors of parasites (e.g., malaria, dengue), emphasizing molecular and quantitative approaches, however.

Currently, there are a limited number of individual researchers at universities or in governmental agencies who train graduate students and/or postdoctoral scholars in tick-related field research. On the other hand, there has been a long-standing interest in the United States in mosquito-borne diseases, and several states have developed outstanding mosquito control programs that are funded by county or state agencies. In California, there are more than 50 mosquito and vector control districts that have funding earmarked primarily for controlling mosquito populations. None of them is engaged in routine tick control. This disconnect favoring mosquito over tick control doubtlessly has to do with the widespread importance of mosquitoes as pests and vectors of animal disease agents in urban and rural areas, their readily discernible and often localized breeding sites in aquatic habitats, and their global importance as vectors of human pathogens. It therefore is not surprising that aspiring vector biologists tend to gravitate toward mosquito research because there are more job and funding opportunities once they complete their training.

VBZD: What can be done to achieve greater support for field focused vector biology research?

RSL: Clearly, more vector biology training centers or programs that offer a balanced curriculum fostering ecological as well as molecular and quantitative approaches for studying vector-borne diseases are essential. More academic and government-funded field-related job opportunities likewise are needed. Besides academia, vector biologists occasionally can find employment opportunities in local, county, state, or federal agencies, or in the U.S. military, but the numbers of field-focused positions advertised annually are few and far between.

There also have to be more opportunities for field-oriented scientists to obtain extramural funding if change is to occur. A more conscious effort should be made by national funding agencies to promote and support field studies because they ultimately form the bedrock upon which any successful field interventions are based. A step in the right direction is the jointly funded NIH/National Science Foundation (NSF) ecology of emerging diseases program that has funded some grants involving vector-borne diseases. To obtain further support for field research, senior-level field scientists must expend more time and energy educating and lobbying national program directors or leaders about the importance of their discipline and why it should receive a greater slice of funding appropriations.

VBZD: You have described how the transmission cycles of RMSF and Colorado tick fever in California are different from those in other regions. How would you explain the significance of these discoveries?

RSL: The primary vector of RMSF in the western United States is the Rocky Mountain wood tick Dermacentor andersoni. In California, this tick occurs mainly in northeastern and east-central counties. However, most of the sporadic RMSF cases in recent decades were contracted in western counties outside the known geographic distribution of D. andersoni and some of its typical hosts. In 1974, I began looking for alternative tick vectors and vertebrate hosts of spotted fever group rickettsiae in western California in collaboration with Dr. Richard Emmons and other colleagues at the CSDHS, and with Dr. Robert Philip and Elizabeth Casper at the Rocky Mountain Laboratory in Hamilton, Montana. We detected a remarkably diverse flora of rickettsiae in several human-biting and non–human-biting ticks. Our most exciting finding was that the human-biting Pacific Coast tick (D. occidentalis) harbors an unclassified spotted fever group rickettsia designated 364D, which we incriminated as a probable human pathogen for the first time. Laboratory findings established that 364D is related to Rickettsia rickettsii, the etiologic agent of RMSF in the Rocky Mountain region and the eastern United States.

Our work on Colorado tick fever was done contemporaneously with the rickettsial studies, and it led to the discovery of a variant isolate of Colorado tick fever virus that differed significantly from all previously characterized strains from the Rocky Mountain region. We found antibodies to the virus in several species of mammals and recovered an isolate from a black-tailed jack rabbit. Although occasional cases of Colorado tick fever–like illnesses occur in western California, a region far removed from the geographic distribution of its only known vector to humans (D. andersoni), we were unable to identify the tick vector. These findings underscore the importance for state or federal health authorities to perform routine surveillance activities for vector-borne microbes in order to detect and identify emerging or resurging agents that may be pathogenic for humans.

VBZD: During your career Borrelia burgdorferi became an important pathogen in the United States. You also worked on B. bissettii, which does not seem to cause disease in humans in this country. Can you tell us more about it?

RSL: Borrelia bissettii is a member of the Lyme disease spirochete complex. Marjorie Bissett and her co-worker Warren Hill first isolated the spirochete from a western black-legged tick from northwestern California. In 1998, Danièle Postic at the Institut Pasteur and co-workers, including me, found that this isolate represented a new species of Lyme disease spirochete, and named it in honor of Dr. Bissett.

To date, 16 genospecies of Lyme disease spirochetes have been described and named worldwide, seven of which have been implicated as human pathogens, including B. bissettii in the Czech Republic and Slovenia. Three members of the complex commonly infect people, only one of which (B. burgdorferi) is a proven cause of Lyme disease in the United States.

We have been studying the relationship of B. bissettii to ixodid ticks and their hosts in the field and in the laboratory in parallel with our research on B. burgdorferi and related spirochetes. Many individuals contributed to this body of research, but the Ph.D. studies of my first graduate student, Richard Brown, laid the foundation for subsequent ecologic and molecular work. In northern California, it seems that B. bissettii circulates most intensively in certain chaparral (brushland) habitats in a transmission cycle involving dusky-footed wood rats, Peromyscus mice, and the predominantly non–human-biting tick Ixodes spinipalpis. The western black-legged tick also is an efficient experimental vector of the spirochete. Further, we, along with Dr. James Katzel and colleagues at the CSDHS (Drs. Paul Duffey, Will Probert, and co-workers), have been attempting to determine if B. bissettii sporadically infects people in California. We suspect that it does for multiple reasons: it is widely distributed in California; western black-legged ticks (I. pacificus) are infected naturally with it and this vector infests people more often than any other human-biter in the state; and it is a human pathogen in the two aforementioned European countries.

VBZD: Your work on the ecology of ticks has been instrumental in identifying risk factors for human exposure and has also been important in evaluating different control strategies. How has your work contributed to reducing the impact of ticks on people and domestic animals?

RSL: To share our relevant findings about risky habitats and human behaviors that elevate exposure to vector ticks, as well as efficacious preventive measures, we have engaged in a considerable amount of outreach. These activities have involved publishing pieces in non–peer-reviewed regional or national magazines, giving frequent public lectures, and providing information to the print and broadcast media upon request. A piece I wrote on Lyme disease in California for home gardeners, landscape professionals, and the public is available on the internet. Perhaps the most effective way that I have made our work available to the laity has been through my participation as a member and the first chairperson of the statewide Lyme Disease Advisory Committee. This committee meets twice annually and its charge is to develop public educational materials about Lyme disease and other tick-borne diseases with an emphasis on ecology, epidemiology, and prevention. Some of the materials are intended specifically to educate Californian physicians, school children, or other groups. This committee works in concert with members of the Vector-Borne Disease Section, California Department of Public Health, which it advises. Educational materials in both English and Spanish can be accessed online.

VBZD: What do you perceive to be the most pressing need(s) in vector biology research and particularly in tick research?

RSL: In the interest of brevity, I will confine my comments to public health-related tick research. It is my considered opinion that the most pressing challenges are trying to obtain more governmental support for preventing tick-borne diseases, increasing public awareness, and transferring the extant preventive measures into practical, integrated approaches that will gain greater acceptance by a larger segment of at-risk populations. These kinds of issues were discussed recently by my colleagues Joe Piesman and Lars Eisen in a comprehensive review article (Annu Rev Entomol. 2008; 53:323–343). Government-funded programs for controlling ticks are virtually nonexistent at all levels (county, state, and federal), in striking contrast to what has been spent to control mosquitoes.

The reasons for the dramatic increase in tick-borne diseases during the past three decades are complex: environmental changes that result in greater densities of ticks and some of their primary hosts; land-use changes and human behaviors that raise the likelihood of tick exposure; and the emergence of previously unrecognized tick-borne pathogens. Unfortunately, the few methods available for managing tick populations at the community or regional level have not gained widespread acceptance by the public, and vaccines against the two major tick-borne diseases in the United States (Lyme disease and RMSF) are not commercially available.

On the other hand, considerable success in reducing tick abundance or infection prevalence with Lyme disease spirochetes in the northeastern United States has been realized with such methods as the four-poster device for reducing populations of black-legged ticks that feed on white-tailed deer, with host-targeted methods directed against rodent reservoirs, the timely application of acaricides against questing ticks, or with integrated approaches employing a combination of methods. Without more governmental funding and guidance, however, it is unlikely that these interventions will be adopted for routine use in community settings.

With respect to education, more regional educational campaigns need to be carried out that target both healthcare providers and citizens. In California, some academic physicians and clinicians practicing in Lyme disease endemic areas are either unaware of its occurrence or unconvinced of its importance despite repeated attempts by those of us working in the field to get the word out. To be sure, Lyme disease is not nearly as common an infection in this state as it is in the northeastern and upper midwestern United States. Nevertheless, there are intense regional hotspots, particularly in northwestern counties where in some years local populations of nymphal western black-legged ticks have B. burgdorferi infection prevalences approaching those found in highly endemic areas of the East.

Another imperative, related research need is to continue ongoing research seeking novel methods for controlling ticks. A few recent promising approaches include the use of fungi or natural products as biopesticides and sequencing the genome of vector ticks like the black-legged tick I. scapularis. Genomic methods not only facilitate population genetic studies, but they conceivably could lead to the development of novel approaches for managing tick populations.

Finally, other urgent tick-research needs include clarifying the transmission cycles of emerging, invading, or resurging zoonotic agents, or those of low prevalence with poorly understood cycles but that could be used as agents of bioterrorism. Additionally, we need to use geographical information/remote sensing systems and ground-truthing ecological studies to identify environmental correlates of risk, and to advance molecular research at the tick–host interface to discover bioactive molecules that may lend themselves to novel control methods.

VBZD: How do you view the future of tick-borne diseases in the United States?

RSL: I firmly believe that ticks will continue to remain the most important group of arthropods among those that transmit zoonotic agents in this country. The number of reported cases of emerging or resurging tick-borne diseases has not reached a plateau since the initial recognition of Lyme disease as a distinct clinical entity over three decades ago. In 2007, there were more than 27,400 reported cases of Lyme disease, an all-time high. The number of cases of RMSF has climbed steadily since 2000 and now exceeds 2000 annually, and human granulocytic anaplasmosis and human monocytic ehrlichiosis cases number in the hundreds each year. And the list goes on when one throws into the mix human babesiosis, Colorado tick fever, tick-borne relapsing fever, and tularemia. The latter diseases are not as prevalent as the above, but they nonetheless can be of considerable regional or local public health significance. There always will be a demand for basic tick research, an impetus for developing and implementing novel approaches for managing ticks, and a need for training the next generation of tick researchers.

VBZD: You have had a remarkable track record in funded research, for example 22 years of continued NIH funding for your grant on Lyme disease. What advice would you offer to young researchers to help them obtain funding?

RSL: It indeed is difficult nowadays for many postdoctoral scholars or assistant professors to secure their first sizable extramural research grant, especially by themselves. My advice to young researchers is to seek an academic mentor or current colleague who has had experience studying ticks or other vectors and a strong track record acquiring extramural funding. The bottom line is to pursue your specific research passion as long as there are reasonable funding opportunities in support of it, and to persist until you are successful, even if that means submitting multiple grant applications to the same or different funding sources. Gathering preliminary data and publishing at least a few relevant scientific papers before applying are a sine qua non for success. The grant application should emphasize the novelty of one's research ideas and contain clearly defined, testable hypotheses and highly focused experimental designs. When I first applied to the NIH, I began by writing a modest 3-year proposal in an effort to get my foot in the door, and only in subsequent applications did I apply for larger sums and longer periods.

VBZD: What key questions remain unanswered with respect to Lyme disease?

RSL: There are plenty of unanswered questions despite years of intensive study by hundreds of investigators and thousands of resultant scientific publications. I will mention only a few that come immediately to mind. Some of the key issues relate to infection in humans, such as learning more about the molecular basis of pathogenesis to resolve the vigorous and sometimes acrimonious debate as to whether chronic, persistent infections occur in some patients. Lyme disease is a highly polarized disease in the U.S. medical community because some contend that chronic or persistent infections do not occur or, if they do, they are rare entities; whereas, others believe that such infections are not uncommon presentations in patients experiencing late-stage disease. Advocates for the latter position include some physicians whose clinical practices are devoted exclusively to Lyme disease patients. As a result of this controversy, the diagnosis and treatment of Lyme disease are highly contentious issues, and two standards of care exist in the United States, e.g., those that are proponents of short-term versus long-term antimicrobial therapies.

Identification of host blood-meal sources in questing ticks by means of molecular methods is another area begging further exploration. By testing questing ticks simultaneously for presence of Lyme disease spirochete DNA and host-derived DNA, reservoir hosts can be pinpointed while obviating the use of wild-caught animals to address the same question. Cost-effective interventions can then be directed against the primary reservoir host(s) in a given area, if feasible. In Lyme disease endemic areas, there usually are only one or a few vertebrates—typically rodents and occasionally birds—that serve as primary or secondary reservoirs of infection. Such assays are not easy to develop and optimize, and the best ones have yielded a sensitivity of about 50% for identifying host DNA in Borrelia-infected vector ticks.

Clarifying the significance of co-infections in ticks, wildlife reservoirs, and people is another important research topic. Some of the bacteria or protozoans that infect ticks or vertebrates may suppress or eliminate one another when co-infections occur. In humans, it has been suggested that Lyme disease patients co-infected with some of the other tick-borne pathogens may experience more severe symptoms and be more difficult to treat successfully.

Lastly, the need for community-based ecological studies to enhance our understanding of the transmission cycles of Lyme disease spirochetes (and other tick-borne zoonotic agents) cannot be overemphasized. These kinds of studies can be used to identify weak links in the chain of infection, which in turn can be employed in efforts to control them. We have been carrying out this type of research in California in collaboration with Drs. Rick Ostfeld at the Cary Institute of Ecosystem Studies in New York, Cheryl Briggs at the University of California at Santa Barbara, one of her former graduate students (Andrea Swei), and other researchers. That project, which is being funded by an NSF ecology of emerging infectious disease grant, aims to assess the overall impact of sudden oak death (a fungal-like pathogen killing immense numbers of trees in certain kinds of woodlands) on Lyme disease risk in coastal California.

VBZD: Do you believe there has been adequate research resources invested in Lyme disease prevention in the United States, other than the development of a human vaccine?

RSL: I don't believe that sufficient funds have been, or are being, invested in education, prevention, and control activities. The high success achieved with the U.S. Department of Agriculture's Northeast Tick Control Project using the four-poster technology was documented in the August 2009 issue of Vector-Borne and Zoonotic Diseases (Vol. 9, No. 4). Also, the CDC has done an excellent job of supporting projects targeting Lyme disease prevention. In the early 1990s, that agency initiated a Lyme disease cooperative agreement program in which a portion of the funding was directed toward developing innovative preventive measures. Despite the success achieved as a result of that program, the national incidence of the disease has not declined and the number of reported cases continues to rise. I am unaware of any other government-funded programs that specifically target Lyme disease prevention. For these reasons, education and personal-protective measures have remained the first line of defense for preventing tick-borne illnesses.

VBZD: When we think of ticks, in general, we think of their ability to transmit disease. Do ticks have “good” qualities and a role in ecology?

RSL: You could ask the same question about any parasite, whether it is an endoparasite, ectoparasite, or microparasite. Do they have any redeeming qualities other than providing vector biologists or parasitologists a job, a lifetime of study, and the joy of discovery? That is a difficult question to answer, but I believe that if we understood more about ticks and their interactions with their hosts and microparasites we would find that they do have a role in the balance of nature. In certain years, ticks are so abundant that they may play a role in regulating the animal populations they parasitize by reducing their fitness or exsanguinating them. Little is known about how often vertebrates other than certain avian species utilize ticks as a source of food, however.

Few medical entomologists have studied the impact of tick-borne agents on wildlife. We conducted a study with Columbian black-tailed deer in which we experimentally inoculated naïve animals to ascertain if Lyme disease spirochetes potentially have a negative impact on deer populations. Although the animals injected developed disseminated infections, none of them manifested evidence of clinical Lyme disease. These findings are consistent with what one would expect of an animal species that has had a long-term evolutionary association with a particular pathogen, irrespective of its potential to serve as a reservoir host for that agent.

Before we conclude, I would like to take this opportunity to thank all of my mentors (I have been blessed by having had more than my share), my collaborators at other institutions, and the many past and present members of my research team at UCB, including undergraduate and graduate students, postdoctoral researchers, and technicians, for their much appreciated and highly valued contributions.