- Email: [email protected]
The Internet for Scientists
Letters ( J. Alexander, G.H. Coombs and J.C. Mottram, unpublished). Cysteine proteinases of Leishmania and other trypanosomatids have been viewed as promising drug targets for many years4. The major evidence for this has been that cysteine proteinase inhibitors have antileishmanial and antitrypanosomatid activity5–7. However, the precise target for these inhibitors is not easily defined. Our gene-deletion experiments showing that neither cpa nor cpc are essential would appear to suggest that specific inhibition of the CPA or CPC enzymes may have little therapeutic value. However, discovering that an enzyme is not essential does not necessarily invalidate it as a drug target. The report that inhibition of the major CP of Trypanosoma cruzi led to build up of protein in the Golgi apparatus and cell death, the former apparently being the cause of the latter8, means that even cpa and cpc should not be disregarded as potential drug targets. Nevertheless, of the leishmanial CPs known, CPB appears to hold the most promise for chemotherapeutic attack for although cpb null mutants infect BALB/c mice, which are known to be highly susceptible, they do not form lesions in other more resistant mice strains such as C57BL/6 or SvEv 129 (J. Alexander,
G.H. Coombs and J.C. Mottram unpublished). Thus inhibition of CPB enzymes might slow or prevent parasite proliferation and allow the host immune system to function effectively and prevent disease. It remains to be discovered whether inhibition of one or a few isoenzymes is sufficient for a therapeutic benefit or whether it will be necessary to obtain an inhibitor that is effective against all the isoenzymes expressed in amastigotes. One problem that can be envisaged is that if not all of the CPB isoenzymes are inhibited then selective mutation of the remaining enzymes might give rise to drug resistance rather rapidly. The multiplicity of CPs in L. mexicana and the very high activity of some make this species particularly intriguing for experimental work investigating proteolysis. Other Leishmania species, however, are more widespread pathogens, and clearly it is important to design drugs active against all types of leishmaniasis. The data to date suggest that although not all species contain activities of Type I CPs as high as those in L. mexicana, there are homologous enzymes and genes present. It is important that the approaches developed using L. mexicana are now applied to these other species so that a broad spectrum new antileishmanial drug is obtained.
This work was supported by grants from the Medical Research Council (UK). JCM is an MRC Senior Fellow. References 1 Bart, G. et al. (1997) Mol. Biochem. Parasitol. 88, 53–61 2 Mottram, J.C. et al. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6008–6013 3 Mottram, J.C. et al. (1997) J. Biol. Chem. 272, 14285–14293 4 McKerrow, J.H. et al. (1993) Annu. Rev. Microbiol. 47, 821–853 5 Selzer, P.M. et al. (1997) Exp. Parasitol. 87, 212–221 6 McKerrow, J.H., McGrath, M.E. and Engel, J.C. (1995) Parasitol. Today 11, 279–282 7 Coombs, G.H. and Mottram, J.C. (1997) Parasitology 114, S61–S80 8 Engel, J.C. et al. (1998) J. Cell Sci. 111, 597–606 Jeremy C. Mottram Wellcome Unit of Molecular Parasitology University of Glasgow 56 Dumbarton Road Glasgow, UK G11 6NU Graham H. Coombs Division of Infection & Immunity Institute of Biomedical and Life Sciences Joseph Black Building University of Glasgow Glasgow, UK G12 8QQ
Book Reviews The Internet for Scientists by Kevin O’Donnell and Larry Winger, Harwood Academic Publishers, 1997. £14.50 (pbk)/£30.00 (hbk) (xi + 309 pages) ISBN 90 5702 221 4 When did you last see a typewriter? Or one of those black bakelite dialling sort of telephones (except perhaps as a fashion statement or in an old Hollywood black and white movie)? Times change, and ever more rapidly in the world of information technology. Furthermore, contemporary science depends upon collaboration. Few scientists work entirely on their own and are so isolated that if they own a personal computer they have no idea how to use it to acquire information. Most can obtain help through their institution’s computer department or can find someone to advise, or better still show, them what to do. Students especially, even schoolchildren nowadays, are expert at using computers. As with techniques in general, practice is best, and the way to learn how to use the Internet is explore it. Although finding out for yourself may initially take time, you quickly learn along the way. In the circumstances, writing a book of this kind is a perilous undertaking at best. A guide may be an aid, but it certainly does not need to be more than a tenth the length of this one, which is aimed at scientists in the UK particularly. The possession of an e-mail address is assumed. Thus, their imaginary 252
scientist’s computer is already capable of communicating with others, and it would seem unlikely that it has not already been used to do so. While the authors (rightly) expect some of their information to be out of date – it was written before the now universal use of browsers for navigating around the Internet – they also presume their readers are extraordinarily ignorant: ‘email (pronounced E-mail)’. (How else?) A ‘conclusion’ (about two-thirds of the way through the book) gives the flavour: ‘One of the most important components of the Internet is the sharing of information [some would say that information sharing is THE point] and all of the Internet’s tools must serve to facilitate that exchange, and then die, or get transformed into another form, as some better facilitator comes along. ‘Ere, we didn’t train as philosophers, it just came naturally!’ (Their italics too.)
The style is correctly described in the foreword as ‘jokey’. Its verbosity, which has probably doubled its length, and its facetiousness are irritating: for example, the reader is addressed as ‘chump’, there are mirror sites in ‘jolly old England’ and it is
worth taking ‘a wee jaunt’ into the Usenet. Whimsical fictitious characters and their problems are described, such as an evolutionary psychologist ‘currently examining the impact of environmental contamination on resting psyches’ who does not know what his department is doing and a Professor John St John Realitas, a powerful professor and head of department, who does not know what a website is. This book is supposed to help them. One can only wonder at what kind of scientist it is aimed. The facts covered include a 48-page index to scientific mailing lists, a description of Usenet newsgroups, a brief outline of a virtual reality electronic conference, a 20-page review of World Wide Web science sites, a chapter on File Transfer Protocol (FTP) and one on creating your own Web site, which some people might find worth a glance. It is pleasing to see BIONET (who run the newsgroup on parasitology monitored in this journal) described as an ‘oasis of sanity for biologists’. BIONET also runs mailing lists on immunology, glycoscience and C. elegans, which might interest some parasitologists. All a scientist ever really needs to know can be found in 15 pages in the Trends Guide to the Internet, which was updated in September 1997. For further information and pricing, contact Thelma Reid at [email protected] Janice Taverne [email protected]
Parasitology Today, vol. 14, no. 6, 1998
G.H. Coombs and J.C. Mottram unpublished). Thus inhibition of CPB enzymes might slow or prevent parasite proliferation and allow the host immune system to function effectively and prevent disease. It remains to be discovered whether inhibition of one or a few isoenzymes is sufficient for a therapeutic benefit or whether it will be necessary to obtain an inhibitor that is effective against all the isoenzymes expressed in amastigotes. One problem that can be envisaged is that if not all of the CPB isoenzymes are inhibited then selective mutation of the remaining enzymes might give rise to drug resistance rather rapidly. The multiplicity of CPs in L. mexicana and the very high activity of some make this species particularly intriguing for experimental work investigating proteolysis. Other Leishmania species, however, are more widespread pathogens, and clearly it is important to design drugs active against all types of leishmaniasis. The data to date suggest that although not all species contain activities of Type I CPs as high as those in L. mexicana, there are homologous enzymes and genes present. It is important that the approaches developed using L. mexicana are now applied to these other species so that a broad spectrum new antileishmanial drug is obtained.
This work was supported by grants from the Medical Research Council (UK). JCM is an MRC Senior Fellow. References 1 Bart, G. et al. (1997) Mol. Biochem. Parasitol. 88, 53–61 2 Mottram, J.C. et al. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6008–6013 3 Mottram, J.C. et al. (1997) J. Biol. Chem. 272, 14285–14293 4 McKerrow, J.H. et al. (1993) Annu. Rev. Microbiol. 47, 821–853 5 Selzer, P.M. et al. (1997) Exp. Parasitol. 87, 212–221 6 McKerrow, J.H., McGrath, M.E. and Engel, J.C. (1995) Parasitol. Today 11, 279–282 7 Coombs, G.H. and Mottram, J.C. (1997) Parasitology 114, S61–S80 8 Engel, J.C. et al. (1998) J. Cell Sci. 111, 597–606 Jeremy C. Mottram Wellcome Unit of Molecular Parasitology University of Glasgow 56 Dumbarton Road Glasgow, UK G11 6NU Graham H. Coombs Division of Infection & Immunity Institute of Biomedical and Life Sciences Joseph Black Building University of Glasgow Glasgow, UK G12 8QQ
Book Reviews The Internet for Scientists by Kevin O’Donnell and Larry Winger, Harwood Academic Publishers, 1997. £14.50 (pbk)/£30.00 (hbk) (xi + 309 pages) ISBN 90 5702 221 4 When did you last see a typewriter? Or one of those black bakelite dialling sort of telephones (except perhaps as a fashion statement or in an old Hollywood black and white movie)? Times change, and ever more rapidly in the world of information technology. Furthermore, contemporary science depends upon collaboration. Few scientists work entirely on their own and are so isolated that if they own a personal computer they have no idea how to use it to acquire information. Most can obtain help through their institution’s computer department or can find someone to advise, or better still show, them what to do. Students especially, even schoolchildren nowadays, are expert at using computers. As with techniques in general, practice is best, and the way to learn how to use the Internet is explore it. Although finding out for yourself may initially take time, you quickly learn along the way. In the circumstances, writing a book of this kind is a perilous undertaking at best. A guide may be an aid, but it certainly does not need to be more than a tenth the length of this one, which is aimed at scientists in the UK particularly. The possession of an e-mail address is assumed. Thus, their imaginary 252
scientist’s computer is already capable of communicating with others, and it would seem unlikely that it has not already been used to do so. While the authors (rightly) expect some of their information to be out of date – it was written before the now universal use of browsers for navigating around the Internet – they also presume their readers are extraordinarily ignorant: ‘email (pronounced E-mail)’. (How else?) A ‘conclusion’ (about two-thirds of the way through the book) gives the flavour: ‘One of the most important components of the Internet is the sharing of information [some would say that information sharing is THE point] and all of the Internet’s tools must serve to facilitate that exchange, and then die, or get transformed into another form, as some better facilitator comes along. ‘Ere, we didn’t train as philosophers, it just came naturally!’ (Their italics too.)
The style is correctly described in the foreword as ‘jokey’. Its verbosity, which has probably doubled its length, and its facetiousness are irritating: for example, the reader is addressed as ‘chump’, there are mirror sites in ‘jolly old England’ and it is
worth taking ‘a wee jaunt’ into the Usenet. Whimsical fictitious characters and their problems are described, such as an evolutionary psychologist ‘currently examining the impact of environmental contamination on resting psyches’ who does not know what his department is doing and a Professor John St John Realitas, a powerful professor and head of department, who does not know what a website is. This book is supposed to help them. One can only wonder at what kind of scientist it is aimed. The facts covered include a 48-page index to scientific mailing lists, a description of Usenet newsgroups, a brief outline of a virtual reality electronic conference, a 20-page review of World Wide Web science sites, a chapter on File Transfer Protocol (FTP) and one on creating your own Web site, which some people might find worth a glance. It is pleasing to see BIONET (who run the newsgroup on parasitology monitored in this journal) described as an ‘oasis of sanity for biologists’. BIONET also runs mailing lists on immunology, glycoscience and C. elegans, which might interest some parasitologists. All a scientist ever really needs to know can be found in 15 pages in the Trends Guide to the Internet, which was updated in September 1997. For further information and pricing, contact Thelma Reid at [email protected] Janice Taverne [email protected]
Parasitology Today, vol. 14, no. 6, 1998