- Vitro The INVITTOX Data Bank of In
Techniques
in
Toxicology Krys Ungar INVITTOX, Fund for the Replacement of Animals in Medical Experiments, 34 Storney St, Nottingham NG11NB, UK The dissemination of information about methods in in-vitro toxicology is subject to a number of constraints which are identified and discussed, as are the ways in which INVITTOX seeks to address these problems. The continued interest of scientists in INVITTOX suggests that a real gap in information provision is being filled.
Introduction Problems in the transfer of information At each stage in the transfer of scientific information, ’information sinks’ trap the flow of information and cause some to be lost (Table 1). The result is that relevant work may not be identified, or the information received may be inadequate to a specific need. The first sink with the originator of the information, who inevitably will not report all pertinent details. Usually this does not imply any conscious desire to mystify or mislead. Information may be suppressed for reasons of confidentiality, but, more frequently, matters considered irrelevant, uninteresting, or inexplicable are omitted. Further, experiments considered to have failed will not be reported. Thomas Kuhn’ describes ’normal’ science as operating within the framework of a fully accepted paradigm, with research being firmly based on past achievements. Research communications therefore use a professional shorthand, assuming familiarity with the field, its techniques and its literature. Furthermore, they tend to focus on results and potential implications, while skimping on the presentation of methodology so as to leave more space for the discussion. Thus, a scientist wishing to use a new technique may have to piece together its descrip-
Non-communicated information. occurs
Table 1 Information sinks in the transfer of scientific
information.
tion from papers by different authors, only to find that vital details are still lacking.
Discrepancies and modifications. A related problem, concerning methodology, is the tendency to modify experimental systems. This may be intentional, but can also occur by default, e.g. one item may be substituted by another more
readily available. An inadvertent error may give better results than the original procedure. Consequently, one often finds discrepancies, even
amongst the papers of
one
author, in the
descriptions of one method. While this should not occur in the fixed protocol of a validated test system, it is inevitable and desirable in relation systems under development and to more research-oriented methods. One must then determine whether a discrepancy is trivial, or whether it reflects a substantial improvement. to
Too much information. Not only a lack, but also an excess of detail can cause information to be lost within the total mass generated. The following complaint is not new: ’One of the diseases of this age is the multiplicity of books; they doth so overcharge the world that it is not able to digest the abundance of idle matter that is every day hatched and brought forth into the world’
Barnaby Rich 16132 It has been estimated’ that science grows 15 years of any observed parameter, e.g. number of journals, number of abstracts, number of PhDs. The persistence of this trend through wars, recessions
exponentially, with a doubling every
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
152
and other disasters for 200-300 years
seems to
guarantee its continuation. Pressure to publish has caused an avalanche of publications, many of which are of questionable values. A recent study revealed that 41-45%
of papers in biomedicine do not receive a in the first 5 years following single citation 4
scientists identified with the help of ERGATT. A core group was identified of scientists prepared to share information on methods they were using and developing. By mid-1989, when a potentially viable structure existed, INVITTOX was launched in ATLA (Alternatives pean
to
Laboratory Animals).66
.
publication.4
Organization of INVITTOX
Inadequate processing and retrieval of information. Secondary publications and on-line databases attempt to combat this problem. Their coverage is impressive, but pertinent references are not always retrievable due to the difficulty of satisfying diverse information needs within one abstract which must indicate the potential value of the document to a spectrum of users. Indexing expands the information provided and increases searching power, but is limited in the number of facets that can simultaneously be expressed. Thus, within the major biomedical databases, one cannot identify with confidence publications about methodological advances. Furthermore, the retrieval of references over the whole field of in-vitro toxicology requires complex search profiles, due to the multidisciplinary input into this field. Problems of the invisible
The original plan was for the INVITTOX database to contain details of registrations, details of INVITTOX protocols, and bibliographical references to the current literature of in-vitro toxicology. The first two libraries are indexed by means of a unified thesaurus constructed for this purpose. The literature library is currently in abeyance, since experience showed that it required an excessive commitment of time and resources. It was considered preferable to concentrate initially on the production of protocols.
INVITTOX protocols INVITTOX protocols aim to give precise, upto-date technical information on in-vitro techniques, their applications, advantages and drawbacks. Each protocol consists of comprehensive instructions, the rationale behind the technique, an assessment of the accuracy of the system, its
The scientific
sensitivity, facility, shortcomings, performance
community responded to this overproliferation of literature by forming a network of informal contacts: the invisible college.’ Meetings, visits, exchanges of letters and preprints allow a more rapid and directed flow of information, but can
in relation to other systems and a list of references relating to the technique. Where possible, representative experimental data are included. Protocols are produced in collaboration with informants, who, while not necessarily the originators, use the methods regularly and are involved in their development. The informant sends information in the most convenient form, usually as preprints/reprints containing details of the method. INVITTOX staff extract relevant information and produce a draft protocol. Any discrepancies are noted together with points where more detail is needed. The answers to these questions, together with other comments or changes suggested by the informant are incorporated into a new draft. This iterative process continues until both sides are satisfied, at which point the informant clears the protocol for release. This process, although labour-intensive, helps to plug the information sinks discussed above. Non-communicated information, discrepancies and modifications are noted by INVITTOX and resolved in consultation with the informant. INVITTOX, being concerned primarily with the distribution of its own protocols, avoids the losses of methodology in an excess of other documentation and of information through inadequate retrieval mechanisms.
college.
information sinks. The information available depends on the knowledge and memory of one’s contact and can be incomplete or incorrect. Moreover, the invisible college is elitist and expensive, directed at the ‘a$luent scientific commuter’,’ often including only the most senior scientists, who may no longer be active at the bench and may therefore lack awareness of the practical problems being faced. create
The INVITTOX data bank Establishment
of the data bank that difficulty in obtaining adequate methodological information from the published literature is one factor hindering the acAn
awareness
ceptance of in-vitro alternatives to animal-based toxicity tests, led FRAME and ERGATT (European Research Group for Alternatives in Toxicity Testing) to propose an information service on in-vitro systems. In 1988, a feasibility study financed by FRAME and the Commission of the European Communities established the information needs of potential
users
by surveying Euro-
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
153
Protocol contacts All informants are asked if their name and address may appear on the protocol. A positive response allows direct access to a scientist who has either developed or is regularly using the method. Such a personal contact can be invaluable when practical probelms arise, since at the bench the success of a technique can sometimes be influenced by factors as seemingly trivial as the way in which a tube is shaken to disperse
Table 2 INVITTOX
registrations by country.
cells.
Registered users The provision of protocol contacts is one way in which INVITTOX tries to broaden access to the invisible college. A related function is the maintenance of a database of registered users of INVITTOX. Registrants indicate whether their names may be released, thus allowing INVITTOX to provide lists of people working in a given field or using a given technique.
User feedback INVITTOX protocols
are not peer-reviewed, alfrequently based on already refereed documents. However, the best judgement on a technique comes from its users. For this reason, a questionnaire is sent out with each protocol. Protocols will be updated at intervals, so as to incorporate suggestions and criticisms
though they
are
from users. Thus INYITTOX protocols aim to fulfil one of the criteria for scientific information identified by the National Enquiry on Scholarly
Communication,’ namely
promote ’adaptability’, i.e. the maintenance of a responsive attitude to change and the elimination of obsoto
lete methods. The hope is that the protocols will come to mirror the current consensus on the best way of performing a technique, and will thus ease its progress towards validation and regula-
tory acceptance.
Current status The first list of INVITTOX protocols appeared in April 1990.8 Thirty-eight are currently available, with 50 in preparation. Of the total, about 30% relate to cytotoxicity, 25% to carcinogenicity, genotoxicity and mutagenicity, 20% to target organ toxicity, 15% to irritancy, and the rest to environmental toxicity, teratogenicity, and reproductive toxicity. To date, INVITTOX has sent out nearly 1500 copies of protocols in response to requests, arid over 450 registrations have been received (see Table 2), of whom about 31% are from industry, 55% from academic institutions, and the rest from governmental and medical institutions and other organizations.
The continued interest of scientists in the services of INVITTOX proves that a real gap in information provision is being filled. The European Economic Community has become the major source of finance for INVITTOX, while FRAME provides the balance. So far, INVITTOX has operated at no cost to its users.
Future prospects
Register of validation schemes INVITTOX protocols indicate the status of the method, e.g. in-house development, interlaboratory validation, etc. It seemed logical to extend the information provision at INVITTOX into compiling a register of validation schemes concerning in-vitro toxicity tests. This would include details of the sponsoring organization and managers, purpose of the validation, chemical or product spectrum of interest, tests under study, participating laboratories, and a list of relevant publications. An announcement to this effect appeared in ATLA. Information will be collected through ERGATT and any other individuals or organizations who wish to collaborate in this project.
Broader protocol coverage At the FRAME conference on alternatives in toxicology,’ the importance of establishing the mechanisms that underlie toxic processes was constantly reaffirmed. This implies a need for alternative non-animal methods to study these mechanisms. INVITTOX wishes therefore to include more research-oriented protocols, while understanding that the procedures for such techniques cannot be as tightly defined as those for toxicity test systems.
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
154
’
Conclusions The INVITTOX concept is simple, but demonstrates the benefits of a small-scale operation providing value-added information for a targeted user group, whose needs have been identified. The labour-intensive nature of the work aruges against INVITTOX being commercially viable as an independent entity, even if charges were introduced. This problem is presently solved by financial support from the Commission of the European Communities and
References
FRAME. INVITTOX may at some point have to diversify into wider, less specific information provision in order to subsidise the production of protocols. It is important, however, that INVITTOX survives as a provider of information not otherwise readily available from the literature of in-vitro toxicology.
Acknowledgements Many thanks
to my
colleagues Karen Atkinson and
Saah Steer for their support in
running INVITTOX.
.
1 Kuhn TS. The route to normal science. In: The structure of scientific revolutions, 2nd edn (International encyclo-
pedia of unified science, vol. 2, no. 2), pp. University of Chicago Press, 1970.
10-22.
Chicago:
2 De Solla Price D. Invisible colleges and the affluent scientifc commuter. In Little science, big science, pp 62-91. New York: Columbia University Press, 1965. 3 De Solla Price, D. Prologue to a science of science. In Little science, bigh science, pp 1-32. New York: Columbia University Press, 1965. 4 Hamilton DP. Research papers: who’s uncited now? Science 1991; : 25. 251 5 Gray J & Perry B. The pattern of scientifc communication. In: Scientific Information (Science and Engineering Policy Series), Oxford: Oxford University Press, 1975.
6
Warren M, Atkinson K & Steer S. Introducing IN VITTOX, the ERGATT/FRAME in-vitro toxicology data bank. ATLA 1989; 16: 332-43. Scholarly communication: The report of the National En7 quiry. Baltimore and London: The John Hopkins University Press, 1979. 8 Ungar K, Atkinson K & Steer S. INVITTOX Protocols. ATLA 1990 : 407-10. 17 9 Balls M, Southee JA & Bridges JW (eds). Animals and alternatives in toxicology -present status and future prospects : Proceedings of an international conference to consider the Second Report of the FRAME Toxicity Committee, held at the Royal College of Physicians, London on 12-13 November 1990. London: Macmillan, and New York; VCH Publishers, in preparation.
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
Techniques
in
Toxicology Krys Ungar INVITTOX, Fund for the Replacement of Animals in Medical Experiments, 34 Storney St, Nottingham NG11NB, UK The dissemination of information about methods in in-vitro toxicology is subject to a number of constraints which are identified and discussed, as are the ways in which INVITTOX seeks to address these problems. The continued interest of scientists in INVITTOX suggests that a real gap in information provision is being filled.
Introduction Problems in the transfer of information At each stage in the transfer of scientific information, ’information sinks’ trap the flow of information and cause some to be lost (Table 1). The result is that relevant work may not be identified, or the information received may be inadequate to a specific need. The first sink with the originator of the information, who inevitably will not report all pertinent details. Usually this does not imply any conscious desire to mystify or mislead. Information may be suppressed for reasons of confidentiality, but, more frequently, matters considered irrelevant, uninteresting, or inexplicable are omitted. Further, experiments considered to have failed will not be reported. Thomas Kuhn’ describes ’normal’ science as operating within the framework of a fully accepted paradigm, with research being firmly based on past achievements. Research communications therefore use a professional shorthand, assuming familiarity with the field, its techniques and its literature. Furthermore, they tend to focus on results and potential implications, while skimping on the presentation of methodology so as to leave more space for the discussion. Thus, a scientist wishing to use a new technique may have to piece together its descrip-
Non-communicated information. occurs
Table 1 Information sinks in the transfer of scientific
information.
tion from papers by different authors, only to find that vital details are still lacking.
Discrepancies and modifications. A related problem, concerning methodology, is the tendency to modify experimental systems. This may be intentional, but can also occur by default, e.g. one item may be substituted by another more
readily available. An inadvertent error may give better results than the original procedure. Consequently, one often finds discrepancies, even
amongst the papers of
one
author, in the
descriptions of one method. While this should not occur in the fixed protocol of a validated test system, it is inevitable and desirable in relation systems under development and to more research-oriented methods. One must then determine whether a discrepancy is trivial, or whether it reflects a substantial improvement. to
Too much information. Not only a lack, but also an excess of detail can cause information to be lost within the total mass generated. The following complaint is not new: ’One of the diseases of this age is the multiplicity of books; they doth so overcharge the world that it is not able to digest the abundance of idle matter that is every day hatched and brought forth into the world’
Barnaby Rich 16132 It has been estimated’ that science grows 15 years of any observed parameter, e.g. number of journals, number of abstracts, number of PhDs. The persistence of this trend through wars, recessions
exponentially, with a doubling every
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
152
and other disasters for 200-300 years
seems to
guarantee its continuation. Pressure to publish has caused an avalanche of publications, many of which are of questionable values. A recent study revealed that 41-45%
of papers in biomedicine do not receive a in the first 5 years following single citation 4
scientists identified with the help of ERGATT. A core group was identified of scientists prepared to share information on methods they were using and developing. By mid-1989, when a potentially viable structure existed, INVITTOX was launched in ATLA (Alternatives pean
to
Laboratory Animals).66
.
publication.4
Organization of INVITTOX
Inadequate processing and retrieval of information. Secondary publications and on-line databases attempt to combat this problem. Their coverage is impressive, but pertinent references are not always retrievable due to the difficulty of satisfying diverse information needs within one abstract which must indicate the potential value of the document to a spectrum of users. Indexing expands the information provided and increases searching power, but is limited in the number of facets that can simultaneously be expressed. Thus, within the major biomedical databases, one cannot identify with confidence publications about methodological advances. Furthermore, the retrieval of references over the whole field of in-vitro toxicology requires complex search profiles, due to the multidisciplinary input into this field. Problems of the invisible
The original plan was for the INVITTOX database to contain details of registrations, details of INVITTOX protocols, and bibliographical references to the current literature of in-vitro toxicology. The first two libraries are indexed by means of a unified thesaurus constructed for this purpose. The literature library is currently in abeyance, since experience showed that it required an excessive commitment of time and resources. It was considered preferable to concentrate initially on the production of protocols.
INVITTOX protocols INVITTOX protocols aim to give precise, upto-date technical information on in-vitro techniques, their applications, advantages and drawbacks. Each protocol consists of comprehensive instructions, the rationale behind the technique, an assessment of the accuracy of the system, its
The scientific
sensitivity, facility, shortcomings, performance
community responded to this overproliferation of literature by forming a network of informal contacts: the invisible college.’ Meetings, visits, exchanges of letters and preprints allow a more rapid and directed flow of information, but can
in relation to other systems and a list of references relating to the technique. Where possible, representative experimental data are included. Protocols are produced in collaboration with informants, who, while not necessarily the originators, use the methods regularly and are involved in their development. The informant sends information in the most convenient form, usually as preprints/reprints containing details of the method. INVITTOX staff extract relevant information and produce a draft protocol. Any discrepancies are noted together with points where more detail is needed. The answers to these questions, together with other comments or changes suggested by the informant are incorporated into a new draft. This iterative process continues until both sides are satisfied, at which point the informant clears the protocol for release. This process, although labour-intensive, helps to plug the information sinks discussed above. Non-communicated information, discrepancies and modifications are noted by INVITTOX and resolved in consultation with the informant. INVITTOX, being concerned primarily with the distribution of its own protocols, avoids the losses of methodology in an excess of other documentation and of information through inadequate retrieval mechanisms.
college.
information sinks. The information available depends on the knowledge and memory of one’s contact and can be incomplete or incorrect. Moreover, the invisible college is elitist and expensive, directed at the ‘a$luent scientific commuter’,’ often including only the most senior scientists, who may no longer be active at the bench and may therefore lack awareness of the practical problems being faced. create
The INVITTOX data bank Establishment
of the data bank that difficulty in obtaining adequate methodological information from the published literature is one factor hindering the acAn
awareness
ceptance of in-vitro alternatives to animal-based toxicity tests, led FRAME and ERGATT (European Research Group for Alternatives in Toxicity Testing) to propose an information service on in-vitro systems. In 1988, a feasibility study financed by FRAME and the Commission of the European Communities established the information needs of potential
users
by surveying Euro-
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
153
Protocol contacts All informants are asked if their name and address may appear on the protocol. A positive response allows direct access to a scientist who has either developed or is regularly using the method. Such a personal contact can be invaluable when practical probelms arise, since at the bench the success of a technique can sometimes be influenced by factors as seemingly trivial as the way in which a tube is shaken to disperse
Table 2 INVITTOX
registrations by country.
cells.
Registered users The provision of protocol contacts is one way in which INVITTOX tries to broaden access to the invisible college. A related function is the maintenance of a database of registered users of INVITTOX. Registrants indicate whether their names may be released, thus allowing INVITTOX to provide lists of people working in a given field or using a given technique.
User feedback INVITTOX protocols
are not peer-reviewed, alfrequently based on already refereed documents. However, the best judgement on a technique comes from its users. For this reason, a questionnaire is sent out with each protocol. Protocols will be updated at intervals, so as to incorporate suggestions and criticisms
though they
are
from users. Thus INYITTOX protocols aim to fulfil one of the criteria for scientific information identified by the National Enquiry on Scholarly
Communication,’ namely
promote ’adaptability’, i.e. the maintenance of a responsive attitude to change and the elimination of obsoto
lete methods. The hope is that the protocols will come to mirror the current consensus on the best way of performing a technique, and will thus ease its progress towards validation and regula-
tory acceptance.
Current status The first list of INVITTOX protocols appeared in April 1990.8 Thirty-eight are currently available, with 50 in preparation. Of the total, about 30% relate to cytotoxicity, 25% to carcinogenicity, genotoxicity and mutagenicity, 20% to target organ toxicity, 15% to irritancy, and the rest to environmental toxicity, teratogenicity, and reproductive toxicity. To date, INVITTOX has sent out nearly 1500 copies of protocols in response to requests, arid over 450 registrations have been received (see Table 2), of whom about 31% are from industry, 55% from academic institutions, and the rest from governmental and medical institutions and other organizations.
The continued interest of scientists in the services of INVITTOX proves that a real gap in information provision is being filled. The European Economic Community has become the major source of finance for INVITTOX, while FRAME provides the balance. So far, INVITTOX has operated at no cost to its users.
Future prospects
Register of validation schemes INVITTOX protocols indicate the status of the method, e.g. in-house development, interlaboratory validation, etc. It seemed logical to extend the information provision at INVITTOX into compiling a register of validation schemes concerning in-vitro toxicity tests. This would include details of the sponsoring organization and managers, purpose of the validation, chemical or product spectrum of interest, tests under study, participating laboratories, and a list of relevant publications. An announcement to this effect appeared in ATLA. Information will be collected through ERGATT and any other individuals or organizations who wish to collaborate in this project.
Broader protocol coverage At the FRAME conference on alternatives in toxicology,’ the importance of establishing the mechanisms that underlie toxic processes was constantly reaffirmed. This implies a need for alternative non-animal methods to study these mechanisms. INVITTOX wishes therefore to include more research-oriented protocols, while understanding that the procedures for such techniques cannot be as tightly defined as those for toxicity test systems.
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
154
’
Conclusions The INVITTOX concept is simple, but demonstrates the benefits of a small-scale operation providing value-added information for a targeted user group, whose needs have been identified. The labour-intensive nature of the work aruges against INVITTOX being commercially viable as an independent entity, even if charges were introduced. This problem is presently solved by financial support from the Commission of the European Communities and
References
FRAME. INVITTOX may at some point have to diversify into wider, less specific information provision in order to subsidise the production of protocols. It is important, however, that INVITTOX survives as a provider of information not otherwise readily available from the literature of in-vitro toxicology.
Acknowledgements Many thanks
to my
colleagues Karen Atkinson and
Saah Steer for their support in
running INVITTOX.
.
1 Kuhn TS. The route to normal science. In: The structure of scientific revolutions, 2nd edn (International encyclo-
pedia of unified science, vol. 2, no. 2), pp. University of Chicago Press, 1970.
10-22.
Chicago:
2 De Solla Price D. Invisible colleges and the affluent scientifc commuter. In Little science, big science, pp 62-91. New York: Columbia University Press, 1965. 3 De Solla Price, D. Prologue to a science of science. In Little science, bigh science, pp 1-32. New York: Columbia University Press, 1965. 4 Hamilton DP. Research papers: who’s uncited now? Science 1991; : 25. 251 5 Gray J & Perry B. The pattern of scientifc communication. In: Scientific Information (Science and Engineering Policy Series), Oxford: Oxford University Press, 1975.
6
Warren M, Atkinson K & Steer S. Introducing IN VITTOX, the ERGATT/FRAME in-vitro toxicology data bank. ATLA 1989; 16: 332-43. Scholarly communication: The report of the National En7 quiry. Baltimore and London: The John Hopkins University Press, 1979. 8 Ungar K, Atkinson K & Steer S. INVITTOX Protocols. ATLA 1990 : 407-10. 17 9 Balls M, Southee JA & Bridges JW (eds). Animals and alternatives in toxicology -present status and future prospects : Proceedings of an international conference to consider the Second Report of the FRAME Toxicity Committee, held at the Royal College of Physicians, London on 12-13 November 1990. London: Macmillan, and New York; VCH Publishers, in preparation.
Downloaded from het.sagepub.com at The University of Iowa Libraries on March 13, 2015
