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Mass spectrometry (clinical biochemistry; principles, methods & applications, vol. 1)
422 science' or 'anti-science', whether the public at large (i.e. those who ultimately pay for it all) are enthralled or appalled by the prospect of marvellous 'progress' in science; these are the real determinants. Society's concern flowing from the deaths of 12 children in Bundaberg in 1928 after their immunization against diphtheria with contaminated toxin/antitoxin (covered briefly), or the arrival of the AIDS virus on our shores in the 1980s (too recent to be covered) are much greater stimuli to the relevant areas of medical science, for instance, than any amount of theoretical argument in favour of more basic work on molecular biology or cellular immunology. A second recurring theme follows closely from this. At all times, from the 1788 arrival of the First Fleet to the 1988 policy speeches of the Labour Government, it seems that utilitarian concerns are the ultimate force that drives the scientific engine. Chapter after chapter contains this message: e.g. 'The Aboriginal ancestors had mastered the key problems for subsis-
TIBS 14 - October 1989
tence' (Hiatt and Jones on 'Aboriginal conceptions of the workings of nature'); 'Interest in the botany and zoology of the continent extended only so far as practical utility was involved' in this case mostly collecting unusual specimens that could be sold to European collectors (Jack, 'Cultural transmission: Science and society to 1850'); 'Murchison advised a curriculum for Ballarat based on that of the Royal School of Mines, but modified to emphasize practical mathematics and surveying rather than a complete course of instruction in natural history' (Stafford, 'The long arm of London: Sir Roderick Murchison and imperial science in Australia'); and so on. It would be better to have some progressive policy for the development of science; 'what is missing is the expressed interest of the Government in the development of science in Australia and the Government's conviction that the application of the results of research can aid vitally in the agricultural and industrial development of this country' (from the 1962 Chairman of
A paradigm for the application of Big Science to modern biology Mass S p e c t r o m e t r y (Clinical B i o c h e m i s t r y ; Principles, M e t h o d s & A p p l i c a t i o n s , Vol. 1) edited by A. M. Lawson, Walter de Gruyter, 1989. D M 316.00 (xx + 745 pages) I S B N 3 11 007751 5 This volume affirms that biochemical mass spectrometry (MS) is well into its second golden age, which commenced around 1980. As a result of developments in sample volatilization, magnet design, vacuum technology, electronics and the acquisition and analysis of data, few, if any, types of biomolecules cannot now be usefully analysed by appropriate mass spectrometry techniques. The constraints are now financial: the most interesting potential biochemical applications of mass spectrometry are Big Science and therefore require serious money. The first golden age involved the application of heavy atom labelling techniques to biochemical problems. By 1939, Rittenberg's group were using a home-made mass spectrometer to follow the metabolism of compounds labelled with XSN. Within about ten years, experiments using stable heavy
isotopes had revealed the major metabolic pathways, at least in outline, and there was strong evidence for the identities of some nitrogenous precursors of the purines and haems. In the mid 1940s, the radioisotopes 3H and 14C became more readily available and offered significant advantages for sample preparation and analysis. Hence, despite these early successes, the use of heavy isotopes (and hence biochemical MS) fell into disfavour. For the next 30 years, biochemical MS lagged behind chemical MS. The reason for this is straightforward. Many molecules of interest to organic chemists are moderately volatile and amenable to simple analysis by MS. In contrast, proteins, carbohydrates and nucleic acids and their constituent monomers are hydrophilic, often ionized or zwitterionic structures and therefore non-volatile. Thus the present widespread application of MS to biomolecules had to await the development of suitable methods for producing volatile derivatives or for gentle production of volatile ions from non-volatile samples (e.g. by fast atom bombardment). The present volume is an excellent introduction to the state-of-the-art and
CSIRO, F. W. G. White, quoted in Johnson and Buckley, 'The shaping of contemporary scientific institutions'). 'The development of this country' and 'national needs' are recurring political messages for Australian scientists in 1989. Science is clearly 'now seen as the prime source of technological opportunity'. Returning to the introduction for one final point; we are told that 'this volume had its origins in the deliberations of the Bicentennial History of Science Committee established by the Australian Academy of Science in 1981'. I, for one, sincerely hope that this book, valuable indeed though it is, is not - together with 'two highly successful conferences' - all that the august Academy and its Committee can give us. Two hundred years of science in Australia deserve much more than this. J O H N R. S A B I N E
The University of Adelaide, Waite Agricultural Research Institute, Department of Animal Sciences, Glen Osmond, South Australia 5064.
is strongly recommended as a useful reference source suitable for all biological scientists. Although it forms part of a series on Clinical Biochemistry, it would be a great pity if that title were to discourage potential readers with no clinical interests. Even though many of the examples given in some chapters are chosen for their clinical importance, the general principles are clearly described and the authors have explicitly indicated areas which are not adequately covered, and provided appropriate references. The contributors appear to be well informed and are not afraid to make sensible informed guesses at areas of future progress. In Chapter 1, the editor discusses the main options for each instrument subsystem, i.e. sample introduction and ionization, mass analysis (including a brief section on multi-analyser instruments), ion detection and data processing. His comments on the problems of computer-matching library spectra with those generated in the laboratory indicate that he obviously lives in the real world. He also refers briefly to Fourrier transform MS. Although this technique is still in its infancy, it is considered to have great potential and is likely to be one of the growth areas of the next decade. The range of biochemical MS applications is apparent from the remaining
423
TIBS 14 - October 1989
chapters. These are concerned with specific applications and pay particular attention to the practical aspects of sample preparation. Each of the next 11 chapters deals with a separate group of compounds: These are bile acids, biogenic amines, carbohydrates, lipids, organic acids, peptides (from brain), porphyrins, prostaglandins, purines and pyramidines, steroids and thyroid hormones. The title of Chapter 13, 'Reference Methods', is a term used by clinical chemists to describe analytical procedures which meet defined standards of accuracy but is perhaps not so well known among bioscientists in general. In the final chapter, the present status of classical isotope ratio MS is reviewed. This is, of course, the most direct descendant of the methods used in the 1940s and referred to above. Although the techniques an d apparatus have been considerably updated, the principles remain unchanged. Clinical uses of this methodology are increasing as a result of growing reluctance to risk the hazards of radioisotopes in diagnosis and the relative decrease in cost of heavy isotopes in recent years. Although the book is rLot entirely free from errors, they are not so frequent as to be irritating. Page 14 is probably the worst example, as the key to Fig. 6 is incorrectly numbered from
item 9 onwards. Three lines further down, Reference (20) should probably read (27). The index appears to be reasonably accurate but fails to list certain important topics. For example, sequencing of peptides, carbohydrates and nucleotides is referred to on pp. 431-433, 238-243 and 552-554, respectively, yet only sequencing of the first-named polymer appears in the index. These topics are of considerable and growing importance and additional references to key papers would have been helpful, particularly in the case of peptides. The author emphasizes (p. 446) that MS, though rapid and informative, does not necessarily distinguish between closely related peptides unless used in conjunction with other techniques. The book could be read to advantage by any clinical or academic scientist/ administrator wishing to present the case for establishing advanced collaborative MS facilities for multidisciplinary research and for producing graduates familiar with the modern and sophisticated techniques sought after by industrial employers. Although there is a growing need for low cost instruments to allow clinical laboratories to take advantage of recent developments in MS, many of the most exciting advances have come about through the application of expensive
Coordinating biomolecular data Biomolecular Data, A Resource in Transition edited by Rita R. Colewell, Oxford Science Publications, 1989. £30.00 (xiii + 367pages) I S B N O 19 854247 X In the Introduction to this book reference is given to the discovery in 1983 by Dr Russell Doolittle, and independently by Dr Peter Stockwell, of the sequence similarity between the growth factor PDGF and the v-sis oncogene. This link highlighted to the molecular biology community the value of searching sequence databases to identify inter-relationships between proteins. Since then, there has been an explosion in the number of determined nucleic acid sequences and consequently of protein primary structures. Furthermore, developments in biotechnology and pharmacology, such as protein engineering and rational drug design, have led workers to use a
variety of biomolecular databases, including those of three-dimensional structure, as a central tool in research. The Committee on Data for Science and Technology (CODATA) addressed the problems of coordinating the developments of biomolecular databases. Accordingly, a workshop was held in 1987 to bring together workers in this area. The book is a summary of this meeting with short, easy to read contributions from over 30 contributors. Although the emphasis is on nucleic acid and protein sequences, there are reports on the human gene mapping library, the Brookhaven protein structure database and bibliographic collections. The book is organized into four sections. The first traces the developments that led to the present infrastructure of the databases. The contributors consider the problems that arise due to the rapid growth of data. In 1987 there were o v e r 10 7 nucleotide bases in the
state-of-the-art instrumentation which is available in relatively small numbers of research laboratories. If clinical science and academic research are to exploit and benefit from these advances, solution of the political, financial and organizational problems of sharing high performance MS instrumentation may be at least as important as solving the technical problems. Such multi-user, high cost projects are more familiar to chemists and physicists but it is important that biochemists become involved in similar cooperative arrangements for MS (the same arguments apply to other high cost instruments such as NMR). It is also highly desirable that the next generation of biochemistry students are given the opportunity to meet the skilled technicians who operate MS facilities and be shown how to interpret spectra. Some, at least, of the instructors should have a background in biochemistry and it may be necessary for biochemistry teachers to update their knowledge of MS. With this book on their shelves, they can make a good start on the theory. J. STUART THOMPSON
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK.
GenBank library. If the project to sequence the human genome is undertaken, it is envisaged that by 2005 there will be the sequences of more than 109 bases to store. The second section considers in detail the approach to manage the databases. There are difficulties in data acquisition, quality control, the access of the data and the distribution to outside locations. At present most databases are in serial, fiat files but the use of more sophisticated management systems, such as heirarchical and relational models are explored. The next section focuses on the users of the databases. Examples cited include specific searches for sequence and conformational features in tRNA, DNA and proteins. There is a rapid increase in the number of computer programs that can search a database for complex sequence patterns and biological features. The final section examines future trends. The methods for global exchange of biological data are discussed. Compact disk (CD) ROM is identified as a powerful medium for the future and indeed the developments of
TIBS 14 - October 1989
tence' (Hiatt and Jones on 'Aboriginal conceptions of the workings of nature'); 'Interest in the botany and zoology of the continent extended only so far as practical utility was involved' in this case mostly collecting unusual specimens that could be sold to European collectors (Jack, 'Cultural transmission: Science and society to 1850'); 'Murchison advised a curriculum for Ballarat based on that of the Royal School of Mines, but modified to emphasize practical mathematics and surveying rather than a complete course of instruction in natural history' (Stafford, 'The long arm of London: Sir Roderick Murchison and imperial science in Australia'); and so on. It would be better to have some progressive policy for the development of science; 'what is missing is the expressed interest of the Government in the development of science in Australia and the Government's conviction that the application of the results of research can aid vitally in the agricultural and industrial development of this country' (from the 1962 Chairman of
A paradigm for the application of Big Science to modern biology Mass S p e c t r o m e t r y (Clinical B i o c h e m i s t r y ; Principles, M e t h o d s & A p p l i c a t i o n s , Vol. 1) edited by A. M. Lawson, Walter de Gruyter, 1989. D M 316.00 (xx + 745 pages) I S B N 3 11 007751 5 This volume affirms that biochemical mass spectrometry (MS) is well into its second golden age, which commenced around 1980. As a result of developments in sample volatilization, magnet design, vacuum technology, electronics and the acquisition and analysis of data, few, if any, types of biomolecules cannot now be usefully analysed by appropriate mass spectrometry techniques. The constraints are now financial: the most interesting potential biochemical applications of mass spectrometry are Big Science and therefore require serious money. The first golden age involved the application of heavy atom labelling techniques to biochemical problems. By 1939, Rittenberg's group were using a home-made mass spectrometer to follow the metabolism of compounds labelled with XSN. Within about ten years, experiments using stable heavy
isotopes had revealed the major metabolic pathways, at least in outline, and there was strong evidence for the identities of some nitrogenous precursors of the purines and haems. In the mid 1940s, the radioisotopes 3H and 14C became more readily available and offered significant advantages for sample preparation and analysis. Hence, despite these early successes, the use of heavy isotopes (and hence biochemical MS) fell into disfavour. For the next 30 years, biochemical MS lagged behind chemical MS. The reason for this is straightforward. Many molecules of interest to organic chemists are moderately volatile and amenable to simple analysis by MS. In contrast, proteins, carbohydrates and nucleic acids and their constituent monomers are hydrophilic, often ionized or zwitterionic structures and therefore non-volatile. Thus the present widespread application of MS to biomolecules had to await the development of suitable methods for producing volatile derivatives or for gentle production of volatile ions from non-volatile samples (e.g. by fast atom bombardment). The present volume is an excellent introduction to the state-of-the-art and
CSIRO, F. W. G. White, quoted in Johnson and Buckley, 'The shaping of contemporary scientific institutions'). 'The development of this country' and 'national needs' are recurring political messages for Australian scientists in 1989. Science is clearly 'now seen as the prime source of technological opportunity'. Returning to the introduction for one final point; we are told that 'this volume had its origins in the deliberations of the Bicentennial History of Science Committee established by the Australian Academy of Science in 1981'. I, for one, sincerely hope that this book, valuable indeed though it is, is not - together with 'two highly successful conferences' - all that the august Academy and its Committee can give us. Two hundred years of science in Australia deserve much more than this. J O H N R. S A B I N E
The University of Adelaide, Waite Agricultural Research Institute, Department of Animal Sciences, Glen Osmond, South Australia 5064.
is strongly recommended as a useful reference source suitable for all biological scientists. Although it forms part of a series on Clinical Biochemistry, it would be a great pity if that title were to discourage potential readers with no clinical interests. Even though many of the examples given in some chapters are chosen for their clinical importance, the general principles are clearly described and the authors have explicitly indicated areas which are not adequately covered, and provided appropriate references. The contributors appear to be well informed and are not afraid to make sensible informed guesses at areas of future progress. In Chapter 1, the editor discusses the main options for each instrument subsystem, i.e. sample introduction and ionization, mass analysis (including a brief section on multi-analyser instruments), ion detection and data processing. His comments on the problems of computer-matching library spectra with those generated in the laboratory indicate that he obviously lives in the real world. He also refers briefly to Fourrier transform MS. Although this technique is still in its infancy, it is considered to have great potential and is likely to be one of the growth areas of the next decade. The range of biochemical MS applications is apparent from the remaining
423
TIBS 14 - October 1989
chapters. These are concerned with specific applications and pay particular attention to the practical aspects of sample preparation. Each of the next 11 chapters deals with a separate group of compounds: These are bile acids, biogenic amines, carbohydrates, lipids, organic acids, peptides (from brain), porphyrins, prostaglandins, purines and pyramidines, steroids and thyroid hormones. The title of Chapter 13, 'Reference Methods', is a term used by clinical chemists to describe analytical procedures which meet defined standards of accuracy but is perhaps not so well known among bioscientists in general. In the final chapter, the present status of classical isotope ratio MS is reviewed. This is, of course, the most direct descendant of the methods used in the 1940s and referred to above. Although the techniques an d apparatus have been considerably updated, the principles remain unchanged. Clinical uses of this methodology are increasing as a result of growing reluctance to risk the hazards of radioisotopes in diagnosis and the relative decrease in cost of heavy isotopes in recent years. Although the book is rLot entirely free from errors, they are not so frequent as to be irritating. Page 14 is probably the worst example, as the key to Fig. 6 is incorrectly numbered from
item 9 onwards. Three lines further down, Reference (20) should probably read (27). The index appears to be reasonably accurate but fails to list certain important topics. For example, sequencing of peptides, carbohydrates and nucleotides is referred to on pp. 431-433, 238-243 and 552-554, respectively, yet only sequencing of the first-named polymer appears in the index. These topics are of considerable and growing importance and additional references to key papers would have been helpful, particularly in the case of peptides. The author emphasizes (p. 446) that MS, though rapid and informative, does not necessarily distinguish between closely related peptides unless used in conjunction with other techniques. The book could be read to advantage by any clinical or academic scientist/ administrator wishing to present the case for establishing advanced collaborative MS facilities for multidisciplinary research and for producing graduates familiar with the modern and sophisticated techniques sought after by industrial employers. Although there is a growing need for low cost instruments to allow clinical laboratories to take advantage of recent developments in MS, many of the most exciting advances have come about through the application of expensive
Coordinating biomolecular data Biomolecular Data, A Resource in Transition edited by Rita R. Colewell, Oxford Science Publications, 1989. £30.00 (xiii + 367pages) I S B N O 19 854247 X In the Introduction to this book reference is given to the discovery in 1983 by Dr Russell Doolittle, and independently by Dr Peter Stockwell, of the sequence similarity between the growth factor PDGF and the v-sis oncogene. This link highlighted to the molecular biology community the value of searching sequence databases to identify inter-relationships between proteins. Since then, there has been an explosion in the number of determined nucleic acid sequences and consequently of protein primary structures. Furthermore, developments in biotechnology and pharmacology, such as protein engineering and rational drug design, have led workers to use a
variety of biomolecular databases, including those of three-dimensional structure, as a central tool in research. The Committee on Data for Science and Technology (CODATA) addressed the problems of coordinating the developments of biomolecular databases. Accordingly, a workshop was held in 1987 to bring together workers in this area. The book is a summary of this meeting with short, easy to read contributions from over 30 contributors. Although the emphasis is on nucleic acid and protein sequences, there are reports on the human gene mapping library, the Brookhaven protein structure database and bibliographic collections. The book is organized into four sections. The first traces the developments that led to the present infrastructure of the databases. The contributors consider the problems that arise due to the rapid growth of data. In 1987 there were o v e r 10 7 nucleotide bases in the
state-of-the-art instrumentation which is available in relatively small numbers of research laboratories. If clinical science and academic research are to exploit and benefit from these advances, solution of the political, financial and organizational problems of sharing high performance MS instrumentation may be at least as important as solving the technical problems. Such multi-user, high cost projects are more familiar to chemists and physicists but it is important that biochemists become involved in similar cooperative arrangements for MS (the same arguments apply to other high cost instruments such as NMR). It is also highly desirable that the next generation of biochemistry students are given the opportunity to meet the skilled technicians who operate MS facilities and be shown how to interpret spectra. Some, at least, of the instructors should have a background in biochemistry and it may be necessary for biochemistry teachers to update their knowledge of MS. With this book on their shelves, they can make a good start on the theory. J. STUART THOMPSON
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK.
GenBank library. If the project to sequence the human genome is undertaken, it is envisaged that by 2005 there will be the sequences of more than 109 bases to store. The second section considers in detail the approach to manage the databases. There are difficulties in data acquisition, quality control, the access of the data and the distribution to outside locations. At present most databases are in serial, fiat files but the use of more sophisticated management systems, such as heirarchical and relational models are explored. The next section focuses on the users of the databases. Examples cited include specific searches for sequence and conformational features in tRNA, DNA and proteins. There is a rapid increase in the number of computer programs that can search a database for complex sequence patterns and biological features. The final section examines future trends. The methods for global exchange of biological data are discussed. Compact disk (CD) ROM is identified as a powerful medium for the future and indeed the developments of