Keywords

Introduction

The topic of synergy and value creation, which forms the subject of this chapter, is exemplified brilliantly by Prof. Mir Mulla’s research activities over the past five decades. His contributions span many different insect pests and approaches to controlling these, either in their larval or mature stages, through biological or chemical control. His research covered behavioral and cultural control of eye gnats, development of chemical and biological control tactics for mosquitoes, control of midges and black flies, and pesticide-nontarget organism interactions. He also focused on the biology and ecology of medically important insects, and abundance and distribution of house-dust mites as related to atopic allergy. As a result of this focus on a multitude of organisms, coupled with vast acquisition of broad knowledge of pest control in general, it is not surprising to see the lasting impact and success of Prof. Mulla’s contributions. Several of the other eminent scientists that contributed a chapter to this volume have acquired a similar status and it is interesting to examine the underlying processes leading to their success. Is it their accumulation of knowledge and experience over time? Is their success based primarily on creative abilities and a “feel” for innovation? And perhaps more importantly, is the new generation of young scientists that will be charged with vector research and control in future heading towards a similar status in today’s science world?

We spend very little time trying to understand the factors that drive research that matters – research that really makes a difference in the way we solve pest and disease problems. Contributions that make pest control strategies more cost-effective, socio-economically more acceptable, more environmentally friendly, and indeed more sustainable. For example, of the hundreds of scientific articles that appear every year in the field of malaria vector research, how many of these really change the way we practice malaria vector control in developing countries? Do elaborate models of transmission affect the way we aim to maximise coverage of bednets at villages in remote African settings? Clearly not. Many large-scale trials with nets have established that population effects occur at high coverage rates, and models have shown how dramatic the impact on disease can be (Lengeler 2004). However, of the numerous bednet campaigns currently underway, in how many of these is this knowledge actually being appropriated? How does our knowledge of mosquito population genetics affect control programmes under the responsibility of Ministries of Health and National Malaria Control Programmes? The fact that nearly seven decades of research on malaria vectors has brought us back to the application of more than one million kilograms of DDT in thirteen African nations in 2007 (Sadasivaiah et al. 2007), with possibly more wide-scale use in 2008, begs the question if research efforts are having the right focus and are really designed to deliver contributions aimed at solving the malaria crisis.

During the symposium to commemorate Prof. Mulla’s long-term contributions to vector research and control, we used two quotes to highlight this observation. The first is from Abraham Maslow, who coined the phrase “If a hammer is the only tool you have, you tend to view all problems as nails”. We added a famous quote from Albert Einstein: “If you do what you did, you get what you got”. These statements underscore the danger of incremental approaches to innovation. In the field of vector control this could mean our unchanging focus on insecticides. In spite of knowing that application of insecticides will always lead to resistance, we keep on searching for new compounds – the hammer is the insecticide, all pests are nails. And yes, if you spray against a pest, you will get what you got, resistance. A good example of this approach is the Innovative Vector Control Consortium (IVCC; Hemingway et al. 2006) with its focus on the discovery and development of new public health insecticides. Apparently there is a greater interest in developing strategies to deal with the aftermath of resistance (Kelly-Hope et al. 2008) than to avoid it in the first place by leaving the hammer for what it is and try out new tools.

A further problem relates to the wide-spread availability of and easy access to information, leading to convergence of ideas which undermines creative thinking. Logical incrementalism (Quinn 1978), in which small and seemingly sensible steps are made in the developmental process is the result of knowledge convergence. Radical thinking that leads to transformational change is thus inhibited – any new student in the lab first receives a pile of articles on the subject he/she will be working on. Convergence of thought rather than exploiting the opportunity of radical thought development driven by the simple concept of “becoming smarter by knowing less” (Claxton 2001).

The Death of Creativity

Creativity is made up of three components; expertise, motivation, and creative thinking skills (Fig. 1) (Amabile 2001). Expertise reflects knowledge, which can be present in many different forms (technical, procedural, patents, etc.). Motivation also knows many different forms, but can broadly be grouped into intrinsic (e.g. drive, passion) and extrinsic (e.g. money, work environment, freedom) motivation. Intrinsic motivation is often the major contributing factor for scientists (“I’m not in it for the money”) and is fortunately the component that can easily and immediately be influenced by the work environment.

Fig. 1
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The three components of creativity (after Amabile 2001). Creativity is optimal if the three components are present and integrated

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Considering the more wide-spread availability of information and expertise, coupled to the fact that motivation remains central in the scientific world and is considered a key driver for innovation, it is not surprising to observe that the only remaining option to differentiate is the ability to think creatively. And this is, regretfully, the one component we often ignore or worse, actively inhibit. For example, at present, funding agencies not only expect us to define our goals clearly, but also insist on seeing the path that will be taken to reach those goals. Often to the level of objectives, activities, and let’s not forget the verifiable indicators. There is hardly a better way to remove the challenge for a student that joins such project than by forcing him/her to stick to predefined work plans. The freedom on how to reach goals is thus removed and creative thinking skills shut-off. The net result of this approach is often leading to tunnel vision – the student focuses on the end goals without consideration for observations and processes encountered on the way. Convergence of knowledge, logic incrementalism and tunnel vision are now influencing the innovation process to such extent that major gaps between the disciplines making up a field can no longer be bridged. Genetic control of disease vectors provides a good example of this, where the interface between the modern biotechnological approaches taking place in developed country laboratories are too distant from real-life settings in disease-endemic countries to remain meaningful (Knols and Louis 2006).

Besides challenge and freedom, there are four more inhibitors of creativity (Amabile 2001): resources, group features, and supervisory and organisational support. Many of us spend considerable time being fairly successful in channelling our creativity into resource acquisition rather than using that creativity in our research endeavours. The latter three components are heavily affected by organisational culture (“the way we do things around here”). Again, there isn’t much positive to report when competitiveness in terms of where a paper is published but not the appropriation of knowledge generated is the driving factor for status and career progression within research environments and academic institutions. A further constraint is the fact that research groups normally consist of like-minded individuals. Thus we have a department of entomology and a department of chemistry. However, the assembling of homogenous groups with similar interests has frequently been shown to be the groups with the lowest levels of innovation and creativity. Similar mind-sets don’t deliver grand new ideas. Finally, since work loads are linked to predefined outputs and milestones speed becomes the universal “good”, and as we cannot speed up innovation this often translates in extra time at the lab. Stress becomes the norm, and is a most powerful suppressor of innovation. Then, as the stakes get higher and the need to problem solving intensifies the originality of the result lessens, often becoming stereotyped and uncreative. Given these constraints to creativity, it is hardly surprising that the overwhelming majority of research papers produced every year are incremental at best and that indeed we’re back to where we were: DDT. How can this be improved?

Synergy and Value Creation

In his landmark book, The structure of scientific revolutions, Thomas Kuhn (1962) detailed nicely that almost any breakthrough in scientific endeavor is first a break with tradition. A classical example is penicillin: fungal contamination of petri dishes wasn’t just contamination nor was it that Fleming planned experiments that led to the discovery. But it was the discovery of antibiotics that saved millions of lives since. It is the challenge and opportunities to obtain intrinsic and extrinsic rewards that will drive young creative scientists to certain research domains. Regretfully, in the field of vector control and research, this domain is dominated by both high-tech and modern biotechnological approaches. It is apparently considered sexier to work with micro-arrays than to use a dipper to collect larvae in breeding sites in rural Africa. Youngsters may even consider that all the basic questions of field biology in malaria and other vector-borne diseases have been solved and that this domain is therefore no longer exciting and perhaps even boring. The contrary is true.

The disparity between research in the developed world and that going on in disease-endemic countries is, however, a point of concern. An army of students in Europe and the USA, for which I coined the term “Eppendorf generation”, is, out of necessity, focused on the minutia, without developing the ability to see malaria as a real disease that is out there killing a child every 30s. Curtis (2002) made the case by arguing that further work in molecular entomology should be driven by the practical problems that vector control personnel has, not by what molecular biologists can and would like to do with new technological developments in the field of molecular biology.

Synergy and value creation offer good opportunities to regain focus and search for innovative solutions to old problems:

  • Synergy is venturing beyond disciplinary boundaries to seek scope economies; it is fundamental research. Vector biologists looking at pest control in agriculture, looking at the developments in medicine, looking at developments in internet and communication technology – how can we use what is already out there creatively to advance our own discipline?

  • Value creation deals with moving research from the bench to the field; it is operational research. How can we ensure that our research efforts actually reach the field and contribute to a reduction in disease morbidity and mortality (like in the case of malaria)?

Neither of this is easy as it requires a change in the context in which we work (Fig. 2). We need to start thinking big – do what Bill Gates did when he envisioned the world connected by computers in the 1980s. Instead of running the next gel, let’s think what the actual contribution of that gel to problem solving will be. Rather than marvel at our latest paper in Science or PNAS, should we not be more concerned about the appropriation of that knowledge? What does it actually do to solve the problem? And finally, how can we release our students to become transformational thinkers?

Fig. 2
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Changing the conceptual framework in which we operate, to drive creativity, innovation, and transformational change

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Contemporary research in medical entomology today operates like the top row in Fig. 2. There is focus on details, incremental developments, and frequently the search for publishable results, with a minimal outcome. We’ve become used to publishing findings and make small contributions although recently there have been moves towards working in line with the bottom row of Fig. 2. A great example is the Bill & Melinda Gates Foundation’s Exploration scheme (Anonymous 2008a), which has been designed to encourage synergy in order to radically change the development process, break with traditional funding mechanisms, and involve scientists not directly working on tuberculosis, HIV, malaria etc. to apply their knowledge to these diseases and generate new ideas and approaches (Roberts and Enserink 2007). Likewise, new funding mechanisms based on submission of tenders to solve specific problems and involve anyone in society are underway (Travis 2008). Whether or not such initiatives will yield radically new ways to conduct vector control remains to be seen, but these certainly provide a platform for lateral thinking that drives synergy.

It is interesting to note that “breaking with tradition” has been successfully applied in the field of pest control. The advent of synthetic pyrethroids for the control of agricultural pests led to their initial application on bednet material (Darriet et al. 1984). With hindsight, this example of synergy is perhaps the most significant contribution to malaria vector control (certainly in sub-Saharan Africa) of the last 25 years. The seemingly simple thought of applying an insecticide to a bednet (transformational in itself) now forms the bedrock of protection from malaria with millions of nets being produced and distributed each year; true value creation (Lengeler 2004). We have discussed this example with various peers and combined with classical studies by De Meillon in South Africa in the late 1920s (De Meillon 1936), on house-entry and exiting of mosquitoes, which led to the development of indoor residual spraying, we concluded that these are the two publications that form the basis of how we control malaria in Africa today.

A second good example of breaking with tradition is pest control in greenhouses in the Netherlands. Historically, such pests would be controlled with insecticides, with resistance management tactics in place to resolve the recurring problems associated with this approach. In the early 1980s, at the time when more than 90% of all pest control was undertaken with insecticides, Prof. Joop van Lenteren pioneered research to develop powerful pest control tactics using natural enemies and predators of the major pests (e.g. mites, leaf miners). In spite of scepticism with the farmers and relentless opposition from the pesticide manufacturers, we now practice biological control in more than 90% of the greenhouses – the opposite from the situation 25 years ago. The production and sales of natural enemies and predators has become a multi-million dollar industry in Holland.

A third example, which then also demonstrates the feasibility of such paradigm shifts in developing countries, was the development of odour-baited traps and targets to control the tsetse flies in various African countries. This approach differed radically from bush and game clearing and area-wide insecticide application at the time it was initiated by pioneers like Dr. Glyn Vale and colleagues (Vale 1993). The focus here changed from targeting tsetse at resting sites, requiring area-wide application of insecticides, to a focus on what drives tsetse host-seeking behavior. Certainly for the savannah species of tsetse, this has led to highly potent trap-bait systems.

Architecture and Vector-Borne Disease Control

Frank Snowden, in his recent book on the eradication of malaria in Italy (Snowden 2006), described how Celli, in the early 1900s, was extremely successful in controlling malaria transmission simply by adding physical protection to houses. Only 1% of humans occupying such houses contracted disease in the middle of marshes riddled by mosquitoes, whereas hundreds of people in the control group without screens fell ill. Similarly, in the southern USA, screened porches played a significant role in eradicating malaria. Yet we seem to have forgotten about the potential of this method. The synergy here lies in the use of architecture as a discipline to help us design houses in such a manner that they minimize mosquito entry. Lindsay and colleagues (2002, 2003) showed recently how house entry can be controlled by simple changes in design or use of barriers, even without the use of insecticides. Thus, although we tend to think of houses in Africa as simple mud and thatch structures, more and more advanced house designs are seen, particularly in the urban but also in rural environments, where house design and disease control has a real potential, not only for malaria, but also for the control of tuberculosis, upper respiratory infections and diarrheal diseases. The recently coined concept of the “Casa segura”, by Prof. Barry Beaty and colleagues, builds on the same principles of making entire houses and their future designs more suitable to control (vector-borne) diseases. With the major African malaria vectors preferring to feed indoors, there is ample scope to not protect at the individual level (e.g. through bednet use) but at the household level (by making the entire house mosquito proof, or better still, by turning the entire house into a trap). Synergy can also be exploited by using architectural know-how to study airflows inside houses, and in particular how these can be manipulated. Value creation is the use of redirected airflow that contains human odours to a trap into which host-seeking female mosquitoes can be lured. Clearly, with African malaria vectors visiting a “point source” (i.e. the house), there will be many more things we can do to disrupt their contact with human hosts, besides using nets or indoor residual spraying. At present, we know nothing about the actual behavior of mosquitoes after they enter a house, apart from the fact that following blood feeding a considerable proportion remains indoors. Increased understanding of what drives the search for resting sites will enable more targeted application of insecticides (if these exert no excito-repellency) or other control methods. It is appreciated that such behaviors may differ for the various vectors and will depend on geographical and agro-ecological settings, which as a consequence necessitates detailed knowledge on mosquito behavior and ecology. This, in turn, hinders the development of “blanket technology” that can be applied from The Gambia to Djibouti, from Niger to South Africa (like nets or indoor residual spraying).

Genetically Modified Mosquitoes

An excellent example of synergy and a true paradigm shift is the development of genetic control strategies that essentially move away from mosquito population reduction to population replacement with insects no longer capable of transmitting pathogens. The initial synergy originates from studies that succeeded in germline transformation of Drosophila, in the early 1980s (Spradling and Rubin 1982). It wasn’t until 1991, when a now historical meeting was held in Tucson (Anonymous 1991) that the strategy of incapacitating disease vectors through genetic transformation was coined. The thinking here was certainly transformational: rather than killing mosquitoes, let’s replace them with ones that are harmless. It is not surprising, therefore, that this leap in thinking generated enormous interest from both the scientific and funding communities (Fig. 3). The strategic space that was opened up left those in search for incremental improvements of population reduction strategies far behind. Both the National Institutes of Health (NIH) and the World Health Organization (TDR) were captivated by the idea and devoted major resources (both financial and HR wise) to this new endeavor. Although genetic control strategies had been developed against mosquitoes decades before (Curtis 2006), these all focused mostly on population control. Interest in these had waned, because of technical hurdles but surely also because of the problems related to reinvasion and inability to eliminate local populations. The idea then to drive genes that confer refractoriness through populations resolved these issues, thereby increasing its appeal.

Fig. 3
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The GM (genetically modified) mosquito endeavor, which opened up strategic space in vector control and resulted in high appeal to both the scientific and funding community because of its radical deviation from classical approaches

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The synergy resulted in remarkable progress within a decade. Successful stable germline transformation of An. stephensi was accomplished in 2000 (Catteruccia et al. 2000). Just two years later the first transgenic mosquito with much reduced ability to transmit rodent malaria was created (Ito et al. 2002). The value creation of these successes has proven more difficult. To date, no efficient drive mechanism is available, no effector molecules to target human malarias (in particular P. falciparum) have been identified, and GM mosquitoes suffer from fitness losses (Marrelli et al. 2006) although this may be compensated for when mosquitoes are actually being challenged with parasites (Marrelli et al. 2007). Much bigger hurdles are to be expected when moving towards field implementation, in the absence of proof-of-principle under near natural conditions. Although these experiments are now underway (Clayton 2006), it remains uncertain how end-users will view this approach. Not only are ethical, legal and social issues the most neglected aspects of this approach so far, also within the scientific community major scepticism abounds with nearly two-thirds of those asked “will the transgenic mosquito ever fly to control malaria” either answer “no” or “have no opinion” (Knols et al. 2007). It is imperative, therefore, to not only have the operational power to define the future of GM mosquito research, but also have criteria power. These criteria are often defined outside the scientific community yet may have major implications on the ability to further the approach towards full field evaluation. In other words, synergy is more powerful with due consideration of the potential for value creation.

It is interesting to compare this with the development of malaria vaccines. In spite of decades of research, the value creation of this approach has never been questioned because of the grand successes that have been accomplished with vaccination (e.g. smallpox eradication). Without any synergy, all vaccines are after all based on active immunization, the value of the approach remains incredibly strong, even when it is acknowledged that a commercial vaccine may be a decade away at best. What the GM approach lacks is value creation; evidence that in operational as well as biological terms there is a good chance of success.

Larval Control: Forgotten Successes

A significant change in malaria vector control followed MacDonald’s book The epidemiology and control of malaria (1957). The now famous Ross/MacDonald equations on vectorial capacity as the driver for malaria transmission led to the abandonment of a focus on control of aquatic stages in favour of focusing on adult stages. With the adult daily survival rate of vectors as the sole factor in the equation with exponential rather than linear impact, it fitted well with the launch of the Global Eradication Campaign just two years previously that was largely based on application of residual insecticides in the intra-domiciliary domain.

What seems to have been forgotten here are the dramatic successes in controlling malaria by focusing on the control of larval stages. Long before the advent of chemical adulticides, environmental management and application of larvicides (like the arsenic compound Paris Green) was practiced around the world, sometimes at very large scales. Two examples stand out: the eradication of Anopheles gambiae from North-eastern Brazil (Soper and Wilson 1943; Killeen et al. 2002a), and the eradication of An. arabiensis from Egypt (Shousha 1948).

Considering that at present there is renewed interest in, or at least intensified debate on the potential for global malaria eradication, these historical successes should deliver elements for synergy and value creation (Killeen et al. 2002b). The Brazil example, where following the accidental establishment of an African vector led to its spreading over 54,000 km2 within a decade, would, in today’s context, be viewed as an invasion catastrophe that cannot be averted. Actually, the global spreading of the Asian Tiger mosquito, Aedes albopictus, serves as a good example of our times. In spite of the knowledge that this species will invade much of Western Europe (from Italy), there is no concerted and drastic effort to avoid this, but a great effort by vector biologists to document the looming catastrophe in “The first record of Aedes albopictus in…” articles in the Journal of the American Mosquito Control Association.

In spite of the fact that excellent substitutes for Paris Green have been developed in the form of biological agents like Bacillus thuringiensis israelensis, with proven efficacy against African malaria vectors (Fillinger et al. 2003; Fillinger and Lindsay 2006), the uptake of this approach has been limited so far. Where it has been, results have been encouraging (Majambere et al. 2007). Given that no resistance has been found in anophelines against these biologicals, how could Soper eradicate An. gambiae from a huge area in Brasil, but is failure looming in its native Africa? We argue that not the tool (i.e. larval control) but the approach towards value creation can explain this. Rather than the rigorous, military-style, vertically structured campaigns that were executed in Brazil and Egypt, contemporary larval control is organised through participatory, horizontal schemes (Dongus et al. 2007; Opiyo et al. 2007). With community involvement as a (rightly so) prerequisite in any malaria control campaign it should be questioned therefore if community consent would not be adequate, following which implementation of the actual intervention remains in the hands of dedicated control teams. This than leads to the observation that not the control method itself but the management of the implementation of that method becomes crucial. This is where the difference in success between the French and Gorgas in controlling yellow fever and malaria at the Panama Canal originates from. This is why Soper was so successful in eradicating An. gambiae in Brazil, and why Shousha succeeded in eradicating malaria in Egypt. If value creation fails not because of the tool but because of implementation issues than this requires managers, not scientists. This is why mosquito abatement districts in the USA are highly efficient and successful in applying larval control strategies.

We conclude that, based on historical successes in Africa, larval control can be used to eliminate populations of malaria vectors, but that flaws in value creation are the underlying causes for potential failure. Management, not science, holds the key to success. We have always been struck by the success of Coca Cola, Gillette and Fa (soap). In the smallest and remotest villages in Africa these commodities are always present but bednets are nowhere to be found. It is not that bednets are not wanted (there definitely is market pull) but it is simply the distribution and supply chain management, market positioning and advertising that leads to absence in such settings. And that brings us back to synergy: what can those working in science faculties learn from those in business faculties? With perfect traps available to control tsetse and trypanosomiasis, why aren’t these being applied in major parts of Africa? That’s management (resourcing, production, distribution, application), not science.

Synergy and Value Creation at Wageningen University

Given the merits of synergy and value creation described above, at Wageningen University we now aim to institutionalize this approach. In spite of the constraints we face in terms of grant applications (pre-defined goals, milestones, etc.) we try to create an enabling environment that maximizes the chances of innovative discoveries. For instance, the establishment of an innovation platform, through which we invite specialists from completely unrelated disciplines (e.g. the airline and space industry) to drive synergy in the field of medical and veterinary entomology is most rewarding. Similarly, by actively undertaking exercises to unleash creative thinking in our team members, we have embarked on new topics not being researched anywhere else. Below we describe three examples of synergy and value creation that form the basis for ongoing research in our laboratory.

Identification of Attractants for Malaria Mosquitoes

The example of effective odour-baited traps for tsetse flies formed the basis for research in our group to identify human odours that can be used in a similar way to trap African malaria vectors. The immediate problem we stumbled upon in the early 1990s is the fact that humans produce hundreds of volatile organic chemicals (VOCs), any of which could play a key role in attracting host-seeking females. The classical, laborious, time-consuming and costly approach would be to sample these VOCs from humans, identify these using gas chromatography and mass spectrometry and then evaluate the influence of these on mosquito behaviour. Although not aware of it at that time, we applied synergy throughout our research to zoom in on essential compounds driving this behaviour.

First, we abandoned the above-mentioned organic chemistry approach. Instead, we used the short range behavior of mosquitoes as the starting point, by asking ourselves why mosquitoes prefer to bite certain parts of the body. Based on a study conducted by Haddow (1945) in which he observed biting patterns of the African mosquito Aedes simpsoni on volunteers and concluded a preference for biting the face, we set up similar experiments with four different mosquito species. By placing a motionless naked volunteer under a large bednet and introducing hungry females one-by-one into the net, we obtained biting patterns that were far from random. Of the two malaria vector species tested, we found An. atroparvus preferring to bite on the face, and An. gambiae preferring the ankles and feet (De Jong and Knols 1995). We then also determined that An. albimanus prefers to bite the face (Knols et al. 1994). Subsequently, we showed that this preference is odour-based and that the selection of biting sites is governed by VOCs from the preferred sites. In the case of An. atroparvus/albimanus we could change the biting pattern by channelling exhaled breath out of the experimental room; for An. gambiae we could change the pattern by washing the feet of the volunteer with a non-repellent soap containing anti-microbial agents at 30 min intervals (De Jong and Knols 1995). With An. gambiae as our target species, we used this approach to focus specifically on human foot odour from then onwards.

The second, more unconventional, piece of synergy originated from the social stigma associated with foot odour. Rather than focusing on the composition of foot odour, we searched information available from the pharmaceutical industry, which has multi-million dollar efforts to develop products to quench foot odour. It was there that we found the initial links to certain aromas of cheeses closely resembling foot odour. The Dutch word “tenenkaas”, used to describe strong foot odour, and literally meaning “toes-cheese” then led us to evaluate the attractiveness of pinhead quantities of various smelly cheeses in our windtunnel olfactometer. We subsequently incriminated Limburger cheese as highly attractive to the African malaria vector An. gambiae (Knols and De Jong 1996). At that stage we were oblivious as to why we could attract a highly anthropophilic African malaria mosquito to a Dutch dairy product.

The third piece of synergy came from the field of Food Sciences. We embarked on ploughing through literature on cheese manufacturing and came across statements like “Bacteria used in cheese production may have originated from human skin” (Sharpe et al. 1976), and “Cheese smells of feet rather than the reverse” (Jackman 1982). Rather than focusing on the cheese itself, it was apparently the microbial inoculum used to obtain a specific aroma that mattered. Eventually, we postulated that VOCs produced by the coryneform bacterium Brevibacterium linens on the surface-ripening Limburger cheese is closely related to B. epidermidis, a microbe residing in the toe clefts of human feet (Braks et al. 1999). The fourth piece of synergy thus originated from the discipline of microbiology. By the end of 1996 we had reduced the number of lead compounds from >300 to less than 15. Since that time, additional VOCs that influence the host-seeking behavior of this species have been identified, like ammonia (Braks et al. 2001), but overall most of the original lead compounds are still dominating our research efforts (including research in Tanzania and The Gambia).

All of the studies described above were conducted by one of us (BGJK) with Dr. Ruurd de Jong, an electrophysiologist that worked mostly on Colorado potato beetles. His limited knowledge of mosquitoes at the time we started working together certainly led us to become smarter by knowing less. His insightful questioning, based on knowledge about other insects, was a key driver for the four elements of synergy described above.

The process of value creation since that time has shown more difficult. With proven behavioural effects of the lead VOCs in olfactometer and electrophysiology studies, the exact composition and dose of VOCs in blends that can work under field conditions remains laborious (Qiu et al. 2007). Meanwhile, however, worn socks have been shown to effectively trap An. gambiae under semi-field conditions (Njiru et al. 2006; S. Moore and F. Oketch, unpublished data) and in experimental hut trials in The Gambia (M. Jawara, unpublished data) and the search for effective synthetic blends continues.

Toward Biological Control of Adult Mosquito Vectors

Given the problems associated with insecticide resistance described above, and the simple fact that at Wageningen University we do not, by default, conduct research on insecticides, we have engaged in the search for suitable alternatives to control adult mosquitoes. The synergy exploited here again originates from the field of tsetse fly control whereby scientists at the International Centre of Insect Physiology and Ecology (ICIPE) in Kenya discovered an entomopathogen suitable for infecting and killing tsetse in the mid-1990s (e.g. Maniania 1998). This prompted us to evaluate the potential of spores of Metarhizium anisopliae to infect and kill An. gambiae and the filariasis vector Culex quinquefasciatus (Scholte et al. 2003). Although the use of fungi to control larval stages of mosquitoes had been the focus of research decades before (for review see Scholte et al. 2004), the use of these against adult mosquitoes was novel. Our very first pilot experiments proved successful and this has since led to broad interest in developing this technology as an alternative means to control vector-borne diseases (Thomas and Read 2007).

Like the initial use of synthetic pyrethroids, widely applied against pest in agriculture, on bednets, the synergy in this example originated from the mere observation that this fungus is known to infect and kill a broad spectrum of insects. We have since evaluated the potential impact of application of fungal spores inside houses in southern Tanzania, and have modelled the impact on malaria transmission (Scholte et al. 2005). With colleagues at the Ifakara Health Research and Development Centre (IHRDC) we are now preparing a large-scale trial encompassing several thousand households. Meanwhile we have also been able to infect the dengue and arbovirus vectors Aedes aegypti and Ae. albopictus with this fungus (Scholte et al. 2007).

The value creation of this novel method to control adult mosquitoes is dependent on a variety of technical and implementation issues (Knols and Thomas 2006). A key concern relates to the persistence of spores once applied inside local houses. However, recent identification of mosquito-killing isolates of Beauveria bassiana has shown spore persistence exceeding 6 months (M. Thomas, pers. comm.), bringing practical application closer. More intricate is the fact that biologicals are still viewed as inferior to chemical insecticides much in the same way natural enemies and predators were viewed in the 1980s in the greenhouse example described before. This in spite of the fact that late-killing fungi (mosquitoes succumb to infections 6–14 post exposure to fungi) have a much reduced chance of mosquitoes developing resistance against these (Thomas and Read 2007). Moreover, it has recently been shown that following exposure to fungus, insecticide-resistant strains of An. gambiae, An. arabiensis, and An. funestus display increased susceptiblility to the insecticides they are fully resistant to, posing fungi as an alternative insecticide-resistance management tool (Farenhorst et al., unpublished data).

At a time when the urge to develop new vector control tools is constantly on the agenda of international gatherings it is encouraging to see that research on fungi is ongoing in four African countries (Ghana, Kenya, South Africa, Tanzania), and mass production is underway in two (Senegal, South Africa), and it is hoped that this will develop into a new strategy that can augment the limited arsenal of tools at hand today.

The Achilles Heel of Malaria

Our last example of synergy and value creation lies outside the field of medical entomology, though it was entomology that started it. In 2003, Dr. Richard Mukabana conducted experiments in Kenya on the attractiveness of humans to An. gambiae, when he observed marked fluctuation in attractiveness depending on the infection status with Plasmodium falciparum (Mukabana et al. 2004, 2007). He was subsequently involved in experiments that demonstrated that children carrying gametocytes (infectious to mosquitoes) displayed increased attractiveness to host-seeking females (Lacroix et al. 2005). The theory that Plasmodium parasites may alter the odour profile of hosts and thus render these more attractive to mosquitoes thus became established.

The synergy here lies in the hypothesis that changes in odour profile may be linked to VOCs present in parasite-infected blood that are different from uninfected blood and that these VOCs may be exchanged with the lung cavity at the alveolar interface. In line with the development of breathalyzers for ailments in the developed world (lung cancer, breast cancer, early detection of heart transplant rejection, tuberculosis) we quickly realized the importance of the availability of such devices for non-invasive and rapid screening of patients for malaria parasites. The advantages are numerous (Knols 2005). In particular, a biomarker for gametocyte carriage would give tremendous power of tackling the infectious reservoir with gametocidal drugs or selective protection of hosts when carrying infectious stages.

Value creation of this idea is currently underway. Given that breathalyzers for alcohol are available online for a mere 30 €, it is striking that this approach has not been tried against major diseases of the poor, including sleeping sickness, leishmaniasis, dengue, etc.

Conclusions

In this chapter we have highlighted some of the pitfalls in current research practices that lead to incrementalism and absence of highly innovative ideas. To a large extent this is determined by the gap between appropriation of knowledge and what is requested from vector biologists in academia (publications, grants, teaching and training). It surfaced that current malaria vector control (nets and indoor residual spraying) is based on just two publications in the last Century. We highlight the importance of synergy and value creation and show how these can drive transformational thinking and development of new concepts in vector control. It is concluded that approaches that worked well in the past (larval control, house improvement) have lost appeal and suffer from flaws in value creation that are largely managerial and not science-based. New approaches, in particular genetic control of mosquitoes, will need due consideration of value creation if these are to evolve into open field implementation. Three examples of lateral thinking and application of synergy and value creation have been presented. More will be needed if we are to tackle the challenges posed by disease vectors in the years to come.