INTRODUCTION
The expansion in the volume of research activity over the last 100 years and the acceleration of technological change that underpins the nature and, to a lesser extent, the quality of the science we do, means that those in science today have little time, or indeed opportunity, for reflection on some of the pioneering efforts within their fields. In many ways this is an inevitable consequence of the sheer volume of published research and the rapid expansion in the numbers of specialist and review journals making it increasingly difficult for scientists to keep abreast of all the developments in their field. Even with the ready availability of online journals, scientists today simply do not have time to capture everything that may be relevant to their research. The restriction of our ‘timeframe-of-reference’ results in most recent publications being characterized by a reference list that stretches back no more than 10 years. There is no doubt that the pace of advance has quickened dramatically, making recent developments perhaps more relevant, but this focused approach is likely to be further compounded by scientists developing citation strategies based on recent publications, in response to government attempts to channel a major component of science funding partly on the basis of bibliometric scores. Time alone will tell if such an approach will allow science to flourish or limit its scope by encouraging conservative approaches and stifling innovation.
So, I was delighted to accept the opportunity to join in a celebration with this Centenary Issue of Parasitology and to look back at some of the science and the people behind schistosomiasis research. Of course, I do this from my own knowledge and experience of working in this field. This is not intended to be a complete history of schistosomiasis research, rather a selective and personal review of what might be considered to be the ‘golden years’ of schistosomiasis research. In addressing the subject I will reflect on some very old work but focus more on the immunology and epidemiology of schistosomiasis, an area in which some of my own contributions have been made.
I should say at the outset that, over many years, schistosomiasis research has been characterized by the same friendship and camaraderie that marks most areas of parasitology research. For schistosomiasis, as in any field, pioneers and champions have had a great influence on the direction research takes. Their successes attracted students and collaborators to their laboratories while at the same time promoting sometimes intense rivalries with competitors. As always, the stimulus for the competition is the drive to be the first to make a significant breakthrough, especially when that breakthrough shows unequivocally that the conclusions drawn from experiments in competitor laboratories have to be reconsidered. Such is the dispassionate search for scientific ‘truth’.
I entered parasitology at a time when research was dominated by studies of animal models of infection (Smithers and Terry, Reference Smithers and Terry1965a, Reference Smithers and Terryb, Reference Smithers and Terryc; Stirewalt et al. Reference Stirewalt, Shepperson and Lincicome1965; Dean et al. Reference Dean1983). Rapid advances in the 1970s and 1980s in our understanding of the workings of the immune system and the ability to manipulate murine genetics and the murine immune system in the laboratory had opened rich avenues for research, providing new approaches that experimenters could exploit to try to throw some light on why schistosomes caused disease and why they were such a challenge for the immune system to overcome. Recombinant DNA technology (Rollinson et al. Reference Rollinson, Walker and Simpson1986) and SDS-PAGE (Laemmli, Reference Laemmli1970; Cordeiro and Gazzinelli, Reference Cordeiro and Gazzinelli1979) and Western blotting (Towbin et al. Reference Towbin, Staehelin and Gordon1979) were beginning to become more routine, though sequencing, even of a single gene, remained problematic and a major achievement when reported (Simpson and Knight, Reference Simpson and Knight1986; Nene et al. Reference Nene, Dunne, Johnson, Taylor and Cordingley1986; Simpson et al. Reference Simpson, Chaudri, Knight, Kelly, Rumjanek, Martin and Smithers1987). The routine application of PCR (Mullis et al. Reference Mullis, Faloona, Scharf, Saiki, Horn and Ehrlich1986) was then at least 10 years away. In an age of ‘systems’ and ‘synthetic’ biology with routine use of microarrays, proteomics, metabolomics and whole genome sequencing, those advances seem now to be rather primitive but at the time they led to an explosion in the possibilities for novel experiments.
Many of the scientists who had made major contributions to schistosomiasis research in the 30 years before I entered the field were still active and influential, and new opportunities for field-based research were on the horizon, there could have been no more interesting time to embark on a research career in parasitology.
HISTORY
But before we explore those exciting times, it would be useful to fill in some of the background about the growth and development of schistosomiasis research in the years following the description of the parasites and the elucidation of their life-cycles. The mid- to late- 19th and early 20th centuries were to some extent the ‘new age’ of parasitology. During this period, the determined efforts of many scientists, including David Bruce, William Leishman, Patrick Manson and Ronald Ross transformed our knowledge of the transmission of parasitic infections and the diseases they caused (Barrett et al. Reference Barrett, Innes and Cox2006). All of these scientists are recognized as the pioneers and giants in the field, even if they are not all regarded as perfect role models.
At a time when the tools of the parasitologist were little more than patient, careful, systematic observation and simple but meticulous experimentation, sometimes aided by a relatively primitive microscope, their discoveries are remarkable. In an age where science is driven often by the latest technological advances, it is worth emphasizing the irreplaceable role of the human element in scientific advances. Nothing can replace asking the right question in the right way and there is no doubt that this generation of scientists asked the right questions and focused their experimental design and observations on answering them.
In the field of schistosomiasis there are many scientists who stand out as having made important contributions but space requires I make a personal selection of some of those works I consider to have transformed the field. I accept that others may have a different view, but this is not intended to be an exclusive or exhaustive selection. Some of the choices will be familiar to many, some perhaps controversial and less well known or seen to be small advances, but most have enabled their peers and later generations of scientists to take the field forward in ways that could not always have been predicted. Of course schistosomiasis research has not taken place in a vacuum. Parallel developments in other fields of parasitology and more widely across life sciences have provided the framework for the work that will be described below.
There is no question that schistosomes have been infecting humans for thousands of years but there is now considerable doubt about the interpretations that have been made in recent years of the records made in ancient times. It is impossible to determine just how much people really knew in the distant past but the detection of schistosome eggs in tissues of ancient mummies is sufficient proof of the long and close association between these parasites and human hosts (Jordan, Reference Jordan2000).
The important breakthrough in understanding these parasites and the diseases they cause came appropriately in Cairo, in 1851, with Theodor Bilharz's description of a ‘hematozoan’ that afflicted the population of Egypt (Bilharz and von Siebold, 1852–53). Bilharz wrote to Carl Theodor von Siebold about his findings realizing that the long, white helminths he had secured from the portal veins were something new. He went on to give a clear description of male and female worms and of the blood in the intestines of the worms. He also recorded the eggs of both S. haematobium and S. mansoni parasites which led to some confusion for many years. The following year he reported what was by then called Distomum haematobium from the urinary bladder of an Egyptian boy who had died from meningitis. The later history of the description of the parasites and the discovery of the life-cycles of the different schistosome species involved contributions from several scientists in the late 19th and early 20th century, including M. von Hemsbach, D. Weinland, T. S. Cobbold, M. A. Pirajá Da Silva, R. T. Leiper, E. Blanchard, Sambon, F. Katsurada, K. Fujinami, H. Nakamura, Y. Miyagawa, S. Yokogawa, K. Miyairi and M. Suzuki. While there remains an element of debate on the timing of some of the events and the sharing of the information, particularly among the scientists working on the distinction between S. mansoni and S. haematobium, it is clear that their work was taking them down convergent pathways (see Warren, Reference Warren1973; Jordan, Reference Jordan2000).
Over the following decades much effort was expended on developing a more precise understanding of the biology of schistosome parasites and in examining the details of infection, migration and development in laboratory animals that would lay the groundwork for an era of experimentation and analysis of immune responses to infection.
IMMUNITY
Schistosomiasis research has always been a relatively small field but there have been a number of occasions when ideas generated within the field have had a much wider impact across parasitology and other fields of biological and medical research. One of these ideas was the dominant hypothesis of concomitant immunity proposed by two of the giants of their time, Ron Smithers and the late Roland Terry (Smithers and Terry, Reference Smithers and Terry1967a, Reference Smithers and Terryb; Smithers et al. Reference Smithers, Terry and Hockley1969). Admittedly, Smithers and Terry borrowed the name from cancer biology but their finding that adult schistosome parasites could survive immune responses generated during their growth and development that were then capable of limiting subsequent infections, captured the imaginations of scientists across the globe. The experiments that demonstrated concomitant immunity were rather elegant but technically demanding worm transfers in rhesus monkeys that normally became totally resistant to infection, with up to 2000 cercariae after single primary exposures to between 100 and 1600 cercariae. Their reports stimulated a flurry of activity into the mechanisms that might be responsible for this unusual biology (Smithers and Terry, Reference Smithers and Terry1965a). This work added weight to an observational study completed 30 years previously by Fisher (Reference Fisher1934) in the then Belgian Congo. He postulated two types of immunity, one that eliminated adult worms ‘alpha’ immunity, and one that prevented the establishment of infection, ‘beta’ immunity. Clearly, a mechanism that prevented hyper-infection and excessive pathology that might limit the life-span of a host might ultimately be in the interest of the adult schistosomes, in terms of their opportunities to reproduce and to be transmitted to new hosts before their host was overwhelmed by massive infection levels and the associated pathology generated by the parasites. Subsequent work led to the discovery that the double outer membrane of adult parasites in the blood, a feature of schistosomes and of other blood-dwelling trematodes (McLaren and Hockley, Reference McLaren and Hockley1977; McLaren et al. Reference McLaren, Hockley, Goldring and Hammond1978), is not present in the cercarial stage but is produced relatively rapidly upon invasion of the skin (Hockley and McLaren, Reference Hockley and McLaren1973). This led to the suggestion that until the double outer membrane is in place the schistosomula may be vulnerable to immune attack. This, coupled with the findings that schistosomes could acquire blood-group antigens (Clegg et al. Reference Clegg, Smithers and Terry1971; Goldring et al. Reference Goldring, Clegg, Smithers and Terry1976, Reference Goldring, Kusel and Smithers1977a, Reference Goldring, Sher, Smithers and McLarenb) and effectively hide from their host's immune system, reinforced the view that the targets for immune attack were the invading schistosomula during their migration in the skin, though Smithers and Terry had amply demonstrated the capacity of the immune system to attack and destroy adult worms (Smithers and Terry, Reference Smithers and Terry1965a). But while adult worms could be readily recovered from the blood, there was no easy way to obtain the large numbers of ‘skin-phase’ schistosomula that would allow them to be studied in the detail that would be required to confirm the features that made them susceptible or that might be used to stimulate responses that could then be directed to prevent their survival, growth and development into adult worms that produced the pathology-inducing eggs.
One of the greatest technical breakthroughs in parasitology in the last 100 years was the successful cultivation of malaria parasites by Trager and Jensen (Reference Trager and Jensen1976). In schistosomiasis research the equivalent was the development of methods to transform cercariae to schistosomulae and to culture them in vitro (Stirewalt, Reference Stirewalt1963; Stirewalt et al. Reference Stirewalt, Minnick and Fregeau1966; Clegg and Smithers, Reference Clegg and Smithers1968; Kusel, Reference Kusel1970). These methods offered researchers the opportunity to investigate the early developmental stages of schistosomes that are found normally within the skin and subcutaneous tissues at the beginning of their migration to the definitive site within their mammalian hosts. Later developments allowed parasites to be radio-isotope labelled with [Se75]-selenomethionine making it possible to monitor the migration of schistosomula at various times after infection (Georgi, Reference Georgi1982, Georgi et al. Reference Georgi, Dean and Chandiwana1982; Crabtree and Wilson, Reference Crabtree and Wilson1986). This was a useful technique but one researcher in London found that storing the [Se75]-selenomethionine in the freezer next to his colleagues' developing autoradiographs was not a way to win friends.
The importance of the artificially-prepared schistosomula is that they allowed both gross and ultrastructural changes in the parasites' membranes to be observed in a way that had hitherto only been possible with adult parasites recovered by perfusion. Even more significant was the ability to culture parasites that would normally be found in the skin together with antibodies and cells recovered from the blood and tissues of infected animals and people. Parallel advances in cell identification and separation technologies made it possible to examine the interaction of specific cell subsets with parasites in a way that would complement the light and electron-microscopical observations and information on the survival and development of parasites in animals that had been immunized against infection by a variety of methods (Vadas et al. Reference Vadas, David, Butterworth, Pisani and Siongok1979). Of course there was a rolling debate about whether schistosomula prepared by allowing cercariae to penetrate an isolated skin preparation were the same as those that would be found in the skin of an infected animal or human, and further debate when it was realized that mechanical transformation by syringe passage could trigger transformation from cercaria to schistosomulum, allowing their use in culture experiments with serum and cells (James and Taylor, Reference James and Taylor1976; Brink et al. Reference Brink, McLaren and Smithers1977).
These developments stimulated a significant research effort. Experiments were designed to exploit these advances and to throw light on the components of the immune system and the mechanisms that were responsible for the partial protection against infection that could be stimulated in a variety of species, with wild-type parasites, Smithers and Terry's ‘concomitant immunity’ – or by multiple doses of irradiation attenuated parasites – the ‘irradiated vaccine’ model. The experiments built on the results and conclusions of earlier investigations in which basic parasitological factors were examined and some in which parasitological results were assessed following cell and serum transfers from infected animals.
It soon became clear that a variety of components of the immune system could attack, damage and destroy schistosomula in vitro but perhaps the most important breakthrough came from the work of Anthony Butterworth and his colleagues. Working in Kenya on Schistosoma mansoni in naturally exposed human populations they demonstrated that in conjunction with antibodies from infected people, white blood cells were capable of damaging schistosomula such that the parasites were unable to maintain their shape and mobility and exclude a vital dye (Butterworth et al. Reference Butterworth, Sturrock, Houba and Rees1974). Fractionation of the blood led to the identification of eosinophils (Butterworth et al. Reference Butterworth, Sturrock, Houba, Mahmoud, Sher and Rees1975) as the critical effector cells in such assays, thus defining, almost 100 years after eosinophils were first clearly differentiated by Paul Ehrlich in 1879, an important and protective function for these relatively mysterious cells that appeared to be associated with helminth infections and allergic pathologies. Once again the finding had implications well beyond the field of schistosomiasis.
Subsequent studies reinforced the view that the immune responses induced by allergens and those induced by helminths might have common features and controls. In science, as with most endeavours, having the good fortune to be in the right place at the right time can be extremely important. I completed undergraduate studies at the University of Glasgow with the extremely good fortune to be taught by Adrian Hopkins, Derek Wakelin, Dean Befus, Bob Bruce, Stephen Phillips, Graham Coombs and Keith Vickerman. This was followed by postgraduate work with Derek on Heligmosomoides polygyrus in a lab with Redwan Moqbel, Richard Grencis, Hassan Alizadeh and Tim Lee. I was completing my thesis at the Wellcome Laboratories for Experimental Parasitology when the MRC advertised a post for someone to work on Schistosoma haematobium in infected populations at their unit in The Gambia with Andrew Wilkins, a brilliant, if at times eccentric epidemiologist and clinician. I do not think anyone, including me, believed I would have had much of a chance of securing the position or that if I did, that I would go, perhaps, not too surprising since the extent of my international travel at that stage of my career was a 5-day break in Paris. The panel at MRC Head Office that included Roland Terry and Brian Greenwood, recommended that I be appointed and I had no hesitation in accepting. All I had to do was finish and defend the thesis, before joining Anthony Butterworth's laboratory in Cambridge to learn the techniques he had been using in his studies in Kenya (Butterworth et al. Reference Butterworth, Capron, Cordingley, Dalton, Dunne, Kariuki, Kimani, Koech, Mugambi, Ouma, Arap Siongok and Sturrock1985, Reference Butterworth, Fulford, Dunne, Ouma and Sturrock1988; Sturrock et al. Reference Sturrock, Kimani, Cottrell, Butterworth, Seitz, Siongok and Houba1983). After 3 months of being mentored by Anthony I left Gatwick on the freezing, foggy morning of 4 April 1981. Stepping off the air-conditioned plane in The Gambia that afternoon, I was not really prepared for the searing blast of hot air from the apron that instantaneously dried every mucous membrane; but it did not take long to adjust and apart from an interruption to the preparations in the first few months due to an attempted coup, not a hazard mentioned by Brian when I was interviewed, work got underway.
Andrew Wilkins' extensive knowledge of epidemiology of S. haematobium in The Gambia and knowledge of Anthony Butterworth's experiences in Kenya, allowed us to draw up plans for a series of studies that would build on Wilkins' own pioneering studies on the transmission of infection and the biology of the parasite in both the snail and human hosts (Wilkins et al. Reference Wilkins, Goll, Marshall and Moore1984a, Reference Wilkins, Goll, Marshall and Mooreb; Goll et al. Reference Goll, Wilkins and Marshall1984). We also benefited from the important studies on egg output stability by David Bradley and Fergus McCullough (McCullough and Bradley, Reference McCullough and Bradley1973; Bradley and McCullough, Reference Bradley and McCullough1973). Anthony Butterworth had realized the value of the newly licensed praziquantel in virtually eliminating schistosome infections from people, opening the way for treatment and reinfection studies which he had initiated in Kenya. The strictly seasonal nature of transmission of S. haematobium in The Gambia meant that we could remove infections from people at a time when there was no prospect of them being reinfected as there were effectively no water bodies containing snails that could transmit the infection (Goll and Wilkins, Reference Goll and Wilkins1984). When transmission started again, our colleague Ursula Blumenthal was able to conduct studies that remain today some of the most detailed and intensive of water contact studies on named individuals ever completed, thus enabling us subsequently to analyse data on levels of reinfection in relation to water contact profiles and immune responses to infection (Wilkins et al. Reference Wilkins, Blumenthal, Hagan, Hayes and Tulloch1987). This work led to the confirmation that, unlike adults, children were susceptible to infection in a way that was water contact dependent; the higher their levels of water contact, the higher their levels of reinfection and of the potential roles for eosinophils (Hagan et al. Reference Hagan, Moore, Adjukiewicz, Greenwood and Wilkins1985a, Reference Hagan, Wilkins, Blumenthal, Hayes and Greenwoodb) and IgE in protection against infection with S. haematobium, offering important evidence that IgE could have an important protective role against helminth infections in humans rather than being associated simply with harmful allergic responses (Hagan et al. Reference Hagan, Blumenthal, Dunn, Simpson and Wilkins1991). The work was effectively a demonstration of the potential protective capacity of IgE in humans and was confirmed for S. mansoni in other epidemiological settings (Rihet et al. Reference Rihet, Demeure, Bourgois, Prata and Dessein1991; Dunne et al. Reference Dunne, Butterworth, Fulford, Kariuki, Langley, Ouma, Capron, Pierce and Sturrock1992). The potential for IgE to protect against schistosome infection had been explored some 30 years earlier when IgE was known as reaginic antibody (Ogilvie, Reference Ogilvie1964; Ogilvie et al. Reference Ogilvie, Smithers and Terry1966; Edwards et al. Reference Edwards, Jones, Smithers and Terry1967). It had taken developments in a number of areas over the intervening period to provide the circumstances for these investigations to take place in an exposed human population.
Ian McGregor's work on transferring adult ‘immune’ serum to children and monitoring its impact on malaria infection is still heralded as being one of the most important developments in the study of malaria immunology. A variation of this study was employed by Joe Cook, Ken Warren and Peter (Pip) Jordan, investigating the immunology of S. mansoni infection, but the details of the protocol for preparation of the serum used in the transfers has been lost, so it is not clear if, in this case, the failure to observe any evidence of protection was due to the absence of IgE removed during the processing of the serum prior to transfer, or some other reason (Warren et al. Reference Warren, Cook and Jordan1972; Cook et al. Reference Cook, Warren and Jordan1972).
As with IgE, the role of eosinophils in protection and pathology remains one of the intriguing paradoxes of immunology. A key feature of the granulomatous pathology in response to the antigens released from schistosome eggs, eosinophils have the capacity to destroy schistosome eggs and miracidial larvae within them, as demonstrated by the beautiful work of Stephanie James and Dan Colley (James and Colley, Reference James and Colley1976; Reference James and Colley1978a, Reference James and Colleyb, Reference James and Colleyc). Further insights have emerged in recent years with an improved understanding of the regulatory role of cytokines during infection.
The goal of most of the immunological studies was to better understand the immunology and pathology of infection with a view to developing a vaccine that could provide protection against infection for use in young children. Proof of concept for vaccination came from the exploitation of irradiated parasites shown to be capable of inducing protection in a wide range of schistosome-host combinations. The most important of these perhaps were the experiments with S. bovis in cattle in The Sudan (Bushara et al. Reference Bushara, Hussein, Saad, Taylor, Dargie, Marshall and Nelson1978) in which it was demonstrated that cattle could be protected against experimental and natural challenge following vaccination with irradiated parasites. André and Monique Capron, and their teams in Lille, building on a vast amount of evidence gathered over many years from pioneering immunological studies in animal models of infection, in natural host-parasite combinations and in populations in endemic areas, made most progress in this area with the production of the glutathione-s-transferase based Bilhvax (Capron et al. Reference Capron, Riveau, Capron and Trottein2005). Perhaps of all groups working on schistosomiasis their contribution has been the most sustained and has had a wider impact on other fields than those of many others. So far, neither Bilhvax nor any of the other many vaccine candidates has made it to the final phase of general release for use in endemic areas but the effort should continue.
DRUGS
Of course, the most significant development in the last 30–40 years is the development, by Bayer, of praziquantel (Gonnert and Andrews, Reference Gonnert and Andrews1977). Praziquantel represented a major advance, as in the early 20th century, after the details of the life-cycle had been determined, intravenous injections of tartar emetic were employed to treat the infection. Tartar emetic was a rather unpleasant drug. Christopherson (Reference Christopherson1918) reported on one of the earliest trials of the effectiveness of tartar emetic in 13 cases he treated in Khartoum and warned of the dangerous consequences to the patient of subacute, acute and chronic antimony poisoning. Now considered to be the drug of choice for the treatment of all variants of the disease caused by the major human schistosome species, it is only in the last few years that praziquantel has been applied on a greater scale across the areas of the world where schistosome infection is endemic Cioli et al. (Reference Cioli, Pica-Mattoccia and Archer1995). The delay in the widespread application of praziquantel for the treatment and control of schistosomiasis is in part due to the extremely high cost of the drug when it was first licensed and marketed after multicentre Phase III trials of praziquantel had been conducted (Davis and Wegner, Reference Davis and Wegner1979; Danso-Appiah et al. Reference Danso-Appiah, Garner, Olliaro and Utzinger2009). In The Gambia, Andrew Wilkins provided some of the evidence of the safety and efficacy of praziquantel with very few reports of side-effects of any significance. The exceptionally high cost of praziquantel and his concerns about the longer-term prospect of the possible emergence and spread of resistance to praziquantel led Wilkins to assess the efficacy of combinations of reduced dose of praziquantel and metrifonate. This combination therapy had no more side-effects than full dose praziquantel. With metrifonate costing no more than a few cents, this effectively halved the cost of treatment and offered to prolong the effective life-span of both drugs. With praziquantel just entering the market place, Wilkins found that this success was not warmly welcomed by those seeking to recoup the massive research and development costs of praziquantel, and he was advised as a clinician that he should not be concerned about the costs of the drugs he used on his patients! One correspondent suggested that rather than preventing the development of resistance Wilkins' use of combination therapy would likely accelerate drug resistance. This was an opportunity missed, as at least some countries would have benefited from the faster introduction of praziquantel that a reduced cost of combined treatment may have allowed. However, even if combination therapy had been deployed, and only half of the recommended dose of praziquantel had been used, the cost of the drug would still, at the time, have remained out of the reach of many health care programmes in the countries where it was most needed.
It has taken many years and the end of patent restrictions for praziquantel to become more readily available and more affordable for use within endemic areas, now that it is produced by a number of generic drug manufacturers. The drive now is to extend the availability and use of praziquantel where it is needed most but its value as a control tool has been ably demonstrated as a result of its widespread use in the Schistosomiasis Control Programme in Egypt. Praziquantel was the main control intervention with millions of doses being used in communities in Egypt. The drug was supplemented with focal mollusciciding, which most commentators consider had a relatively limited impact on the success of the programme. But the programme was a major success and, even after the first 10 years of the intervention, provided clear proof that a drug-based approach to control was feasible and could be highly effective (Barakat et al. Reference Barakat, Farghaly, El Morshedy, Hassan and Miller1998). There is no question of the immense benefit to the Egyptian people of this programme. However, the repeated interventions that characterized the programme had little impact on transmission in some areas since infection levels in new cohorts of children entering school remained relatively unaltered.
DIAGNOSIS
Routine parasitological diagnosis in field settings and during control programmes is likely to remain the standard Kato-Katz technique for S. mansoni and S. japonicum, with urine filtration for S. haematobium. The limitations of the Kato-Katz have been well rehearsed but it has proved of great utility in all endemic settings and there are few simpler and effective diagnostics that can be so readily applied with such limited training. In Glasgow, we are proud of the pioneering work on the medical applications of ultrasound by Professor Ian Donald M. D. and his colleagues, working at the University of Glasgow's Department of Midwifery. The use of ultrasound in obstetrics and gynaecology opened the way for its use as a diagnostic tool in other medical applications and led to improvements in the technology that have benefited many disciplines. For the study of the pathology of schistosomiasis, portable ultrasound offers many advantages and, while it cannot provide a routine functional assessment in the way that is possible with the transportable isotope renography apparatus, Wilkins (Reference Wilkins, Amuasi, Crawley and Veall1985) used it successfully to measure kidney function in S. haematobium-infected people in The Gambia. Ultrasound is non-invasive and well received by patient populations. The standardization of the ultrasound patterns to enable less-qualified staff to interpret sonographs was a massive step forward in schistosome diagnosis and with the declining cost of high specification portable Doppler ultrasound devices there is likely to be wider use of this technology, although it may still remain limited to some of the larger clinical facilities (Hatz, Reference Hatz2001).
HIPPOPOTAMI!
It would be fair to say that Parasitology was not the journal of choice for much of the work that has been published on schistosomes. Indeed between 1946 and 1970 papers on schistosomes were relatively rare, but the journal is marked by the diversity of material it covers. One of my favourite papers on schistosomiasis published in the journal during this period is one by June Thurston, who spent some of her career in Glasgow, describing Schistosoma hippopotami, in which it is reported that
‘The specimens of S. hippopotami were collected in 1958 by Mr Alan Brooks, game biologist, from the hepatic vessels of a freshly killed hippopotamus’ (my emphasis).
Such a shortage of freezer space is a familiar problem to all laboratory workers (Thurston, Reference Thurston1963). Those who are interested may view the schistosomes, in the British Museum (Natural History) in London, as specimens 1962.27.1.
THE FUTURE
These are very exciting times with powerful technologies capable of allowing us to address problems in new ways but I have a concern that we might no longer be generating scientists with a ‘feeling for the organism’, scientists who have an in-depth knowledge of the detailed aspects of the biology of the parasite they are working on, and of its behaviour in its intermediate and definitive host(s). This may simply be because of the vast amount of data that would need to be absorbed to acquire such knowledge but I fear that studies of basic parasite biology with no immediate translational benefit in terms of a health impact through drug or vaccine development are less likely to be funded and as a consequence are not as attractive to young scientists keen to ensure their research is readily fundable.
The drive for translational research is understandable as in the past, even when breakthroughs were made, such as the manufacture and production of praziquantel, they have not been rapidly exploited in the most effective way. The move to exploiting existing tools more effectively is underway and especially important given the re-assessment of the impact of schistosomes on health (King et al. Reference King, Dickman and Tisch2005).
With apologies to those who have been missed – unless we continue to develop dedicated scientists like D. Brown, A. Butterworth, A. Capron, M. Capron, A. Cheever, D. Cioli, D. Colley, D. Dean, A. Deelder, A. Dessein, M. Doenhoff, D. Dunne, A. Fenwick, G. Gazzinelli, S. James, N. Katz, J. Kusel, D. McLaren, K. Mott, D. Rollinson, A. Sher, R. Smithers, V. Southgate, R. Terry, V. Vennervald, F. von Lichtenberg, K. Warren, G. Webb, A. Wilkins, A. Wilson and M. Woolhouse then we will still be writing about the problems of schistosomiasis by the time the journal reaches its third century.
