Research Article: From Tucson to Genomics and Transgenics: The Vector Biology Network and the Emergence of Modern Vector Biology

Date Published: March 31, 2009

Publisher: Public Library of Science

Author(s): Barry J. Beaty, Denis J. Prager, Anthony A. James, Marcelo Jacobs-Lorena, Louis H. Miller, John H. Law, Frank H. Collins, Fotis C. Kafatos, Serap Aksoy

Abstract: None

Partial Text: The research enterprise is often charged with responding to emerging scientific needs and opportunities involving important public health issues. The establishment of the Vector Biology Network (VBN) by The MacArthur Foundation to address critical scientific, research, and human resource needs in vector biology is a model of how to respond to such a charge efficiently and effectively. When the Network was formed in 1989, the resurgence of vector-borne diseases, including malaria and dengue, had revealed critical research and training needs in vector biology. Major knowledge gaps in vector molecular biology and pathogen transmission limited development of new approaches for vector and disease control. The loss of vector biologists/medical entomologists complicated control of these diseases. Members of the VBN, an international consortium of research laboratories, collaborated in the development and application of modern molecular and genetic approaches in vector biology and in the training of a new cadre of scientists capable of developing and applying modern tools to combat these diseases. The VBN exploited the expertise and resources of the consortium institutions, and exceeded all of its milestones, including: development of molecular and genomic approaches in vector biology; genetic transformation of insect vectors; characterization of vector immune systems; identification of molecular and biological bases of vector competence; and exploitation of identified vulnerabilities to interfere with pathogen transmission. The VBN recruited many established scientists from other fields and trained a new generation of leaders in vector biology. Most importantly, the VBN participated in and helped catalyze a remarkable renaissance in vector biology/medical entomology.

Research on mosquitoes and other arthropod vectors of infectious diseases is of great importance for tackling neglected tropical diseases in the developing world. Vector biology is now a well-established and rapidly advancing field that is providing new understanding of vectors and vector pathogen interactions and creating new opportunities for vector-borne disease (VBD) control. Many key milestones and recruitment and training of new researchers in this field were made possible by the coalescence of several laboratories in the US and Europe into a collaborative research network focused on the biology of disease vectors. The Vector Biology Network (VBN) was established and funded for ten years (1990–2000) by The John D. and Catherine T. MacArthur Foundation. The VBN was reinforced through endorsement and, in some cases, coordinated funding by the World Health Organization (WHO) and national research agencies and foundations, which collectively contributed to a remarkable renaissance of vector biology. The history of the VBN provides a valuable case study of how effective strategies can be developed and deployed to address cost-effectively newly recognized scientific challenges related to important public health and social goals.

The stimulus for developing the VBN was the worldwide resurgence of VBDs. While extraordinary advances in antibiotics and vaccines have controlled many infectious diseases, VBDs continue to afflict hundreds of millions of humans annually, resulting in inestimable morbidity and misery and millions of deaths in disease-endemic countries [1]. These diseases are resurging in areas where they were previously controlled and are newly emerging in other locations. VBD resurgence is associated with multiple causes, including: biological factors such as the lack of efficacious vaccines and therapeutics, development of drug resistance in pathogens and pesticide resistance in arthropod vectors, and limitations on pesticide usage because of safety and environmental concerns; infrastructural factors such as the deterioration of public health systems for VBD surveillance and control, and attrition of scientists and public health practitioners trained in medical entomology or tropical medicine; and demographic and social factors such as rapid population growth, rampant unplanned urbanization in the tropics, and human migration into undeveloped areas containing new pathogens and reservoir hosts for known pathogens.

By the early 1980s, major conceptual and technological advances in molecular biology and genetics were reshaping biomedical research. The manipulation of DNA with recombinant techniques revolutionized the study of gene expression, development, evolution, and population biology. Genetic transformation of Drosophila emerged as a powerful approach to gene identification and characterization in a model arthropod [2]. Rapid progress in the development of inexpensive, widely applicable techniques for gene sequencing fostered genome-wide rather than gene-by-gene approaches in biomedicine. This explosion of molecular technology and knowledge created unparalleled opportunities for rapid advances even in neglected fields; indeed, new molecular studies of pathogens revealed exciting opportunities for development of diagnostics, drugs, and vaccines. However, the study of insect vectors of human disease progressed more slowly for several reasons: (i) the relatively small number of scientists working in the area; (ii) the strong focus of medical entomologists on fieldwork rather than on basic laboratory research; (iii) the historical dissociation in American academia of medical entomology (in schools of agriculture) and parasitology (in schools of medicine), which hindered integration of knowledge on the interaction of parasites with both their human and insect hosts; and (iv) the assumption that new more effective anti-parasite drugs and vaccines were imminent.

The John D. and Catherine T. MacArthur Foundation was established in the late 1970s. Reflecting their personal interests, perspectives on societal needs, and the Foundation’s location in Chicago, the Foundation’s new Board of Directors selected mental health and urban issues for emphasis, and established the MacArthur Fellows Program to recognize and reward extraordinary creative potential in individuals.

Over the next two years, the ideas from that meeting germinated, and led the Foundation to create a new research network focused on vector molecular biology to complement the Parasite Biology Consortium. The Vector Biology Network would include vector laboratories within the Parasite Biology Consortium, and would also exploit newly emerged opportunities. These included the commitment of F. Kafatos to devote 50% of his laboratory to vector biology; the opportunity for A. James, then at Harvard, to start a new vector research program at the University of California Irvine; the convergence of pertinent expertise, infrastructure, and capacity at the NSF-funded Center for Insect Sciences at the University of Arizona; and the establishment of the Arthropod-borne and Infectious Diseases Laboratory at CSU. The VBN laboratories and respective program leaders (PLs) were CWRU (A. Mahowald and M. Jacobs-Lorena), Yale (R. Tesh), Harvard and Crete (F. Kafatos), CSU (B. Beaty), University of Arizona (J. Hildebrand), University of California Irvine (A. James), and NIH (L. Miller). A VBN consortium laboratory was subsequently established at the Centers for Disease Control–Division of Parasitic Diseases, which later moved to the University of Notre Dame (F. Collins).

The VBN was supported by relatively modest funding from The MacArthur Foundation (USD 1.2 million total annually for eight laboratories over ten years) to catalyze and promote the field of molecular vector biology. Yet the impact on vector biology was extraordinary. Metrics of success in this goal include: recruitment of established scientists into the field, research productivity of VBN and its collaborators, training of new vector biologists, vector biology publications in high-quality journals, external funding (largely by NIH-NIAID), and vector biology presentations and sessions at the Annual Meeting of The American Society of Tropical Medicine and Hygiene (ASTMH).

Collaborative research networks were a relatively new phenomenon when the VBN was established in 1989, and represented an experiment in organizing science to tackle some of society’s most significant challenges. For that reason, it is helpful to reflect on the work of the VBN, on how it was structured, and on how it operated. The following thirteen areas represent key lessons from the VBN’s experience.

The VBN more than met the objectives of The MacArthur Foundation, and it validated the field-development concepts that motivated its creation. Through the separate and collaborative research and training activities of Network laboratories, the two-week summer course, and an ongoing set of strategic planning and convening activities, the VBN (i) led in the development of proof-of-concept demonstrations of genetic methods for interrupting the transmission of selected parasitic and viral VBDs; (ii) developed and applied the first methods for producing transgenic mosquitoes; (iii) helped to create the rationale, strategy, and collaborative approach for sequencing the genomes of the most significant mosquito vectors of human malaria and dengue; (iv) produced novel understanding concerning the functions and operation of the insect immune system, illuminated molecular events and vulnerabilities during blood feeding and digestion and the molecular basis of olfaction in host-seeking; (v) developed and offered the BDV course and published the landmark textbook The Biology of Disease Vectors; and (vi) trained more than 600 students, postdoctoral researchers, and faculty from around the world, many of whom now fill leadership positions in vector biology or medical entomology; and (vii) recruited outstanding scientists from other fields to vector biology, many of whom transformed their entire laboratories to work on vectors and have become leaders in the field.



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