Jonas Bergquist (chair), Uppsala University (omvald tom 2024)
jonas.bergquist@kemi.uu.se

Jörg Hanreider, University of Gothenburg (omvald tom 2024)
jorg.hanrieder@gu.se

Leopold Ilag, Stockholm University (omvald tom 2024)
leopold.ilag@aces.su.se

Thomas Kieselbach, Umeå University (omvald tom 2024)
thomas.kieselbach@umu.se

Susana Cristobal, Linköping University (omvald tom 2024)
susana.cristobal@liu.se

Roman Zubarev, Karolinska Institutet (omvald tom 2024)
roman.zubarev@ki.se

Christian Lindh, Lunds University (omvald tom 2024)

Gunnar C Hansson (Styrelsehedersledamot), Göteborgs University (omvald tom 2024)
gunnar.hansson@medkem.gu.se

Protokoll
Masspektrometri Protokoll

Swedish Mass Spectrometry research – some early examples
Compiled by Jan Sjövall in 2010 [Download as pdf]

Coupling high temperature gas‐liquid chromatography with mass spectrometry

Mass spectrometry (MS) entered biochemical research around 1935 as a method for determination of stable isotopes in metabolic experiments with isotope‐labelled compounds. This was the time when the dynamic state of body constituents was revealed and biosynthetic pathways to complex molecules began to be elucidated (ref. 1). In the mid 1940s Einar Hammarsten at the Department of Chemistry, introduced MS at Karolinska Institutet (KI) to analyse stable isotopes in studies of purine and pyrimidine biosynthesis. In 1947 he employed Ragnar Ryhage who became head of the MS‐lab at KI (ref.2). Parallel with the analyses of isotopes and at the request of Einar Stenhagen (at the University of Uppsala) investigating structures of fatty acids and alcohols in tubercle bacilli, Ryhage constructed an instrument for MS of bioorganic molecules. Together these scientists carried out pioneering work on the mass spectrometry of long‐chain fatty acids and alcohols (refs. 3,4). Until this time the predominant use of organic MS had been in the petroleum industry. Gas‐liquid chromatography (GLC) developed by James and Martin (ref. 5) had been rapidly accepted by the biochemists, particularly in the lipid field.

Coupling GLC on‐line with MS, i.e. combining separation with structure determination, became a goal in several laboratories. The packed GLC columns used at the time had carrier gas flow rates in the range of 10‐20 ml/min while the mass spectrometer, operating at high vacuum, could only accept 0.1‐0.2 ml/min i.e. 1 % of the effluent from the GLC column. A method to remove carrier gas with minimal loss of the sample analytes had to be invented. Stenhagen suggested that the principle of the molecule separator, invented by E.W. Becker for isotope separations, could be used and received a patent on the invention (Brit. Pat 1040084). Stenhagen and Ryhage then worked independently on a construction suitable for the combination of GLC with MS at the high temperatures required for GLC separation of compounds in the molecular range of fatty acids and steroids (200‐600 Da). In the separator, the gas stream passes through two holes of small diameter which are very close together where the heavier molecules pass straight through while the carrier gas helium diffuses to the sides of the separator and is pumped away (ref 6,7). To increase the efficiency Ryhage connected two separators in series the first connected to a fore vacuum pump and the second to an oil diffusion pump. The enrichment factor for larger molecules was about 50 and about 50 % of the analytes reached the ion source. A magnetic sector instrument was constructed which permitted fast scanning of the mass range up to 600 Da (ref. 6). Other interfaces for separation of analytes from carrier gas were developed in other laboratories (e.g. ref. 8) but the Becker principle was clearly superior in GC/MS analyses of biomolecules. During the development of the molecule separator Sune Bergström (Nobel Prize in Physiology or Medicine 1982) reached an agreement with Incentive and LKBProducts to manufacture a GC/MS instrument based on a prototype constructed by Ryhage. Jan Sjövall participated in the development, using sterols and bile acids as test compounds to optimize performance with molecules of this size. The first commercially available GC/MS instrument, the LKB 9000, reached the market in 1965. Its impact on many fields of chemistry, biochemistry and pharmacology was great. Among the improvements and additions to the LKB 9000 the AVA (Accelerating Voltage Alternator) should be mentioned (ref. 9). It permitted selected ion monitoring (SIM) or recording (SIR) of a few ions specific for the compound to be quantified and an internal standard labeled with stable isotopes. Swedish pharmacologists headed by Bo Holmstedt working in the same building as Ryhage realized the potential value of this equipment in clinical pharmacology and toxicology, gave the method a name, and published the first application in these areas (ref. 10). Computers soon made the AVA hardware obsolete but the great importance of the method remains in all areas of MS.

Computer systems were constructed early both in Ryhage´s and Stenhagen´s laboratories (see descriptions in the book “Biochemical Applications of Mass Spectrometry” cited in refs 1 and 4). Einar Stenhagen, Sixten Abrahamsson, and Fred W. McLafferty started a collaboration in the early 1960s resulting in the “Atlas of Mass Spectral Data” printed in 1968. Its continuation, the Wiley Registry™ of Mass Spectral Data now has about 600,000 spectra.

Since 30 years, a molecule separator is not needed because of the revolutionary developments of capillary GLC and mass spectrometer instrumentation. A few years after the introduction of the separator, high‐pressure liquid chromatography (HPLC) appeared and attempts were made to couple HPLC with MS. The development of electrospray ionization (by John D. Fenn, Nobel Prize in Chemistry 2002) made todays HPLC‐MS possible. When the first GC/MS instruments appeared it was said that one such instrument would be enough for a medical school. The development of MS illustrates how basic science can change the world of medical research without seemingly having any connection with biology.

Direct‐Inlet EI‐MS Sequencing of Glycosphingolipids

In the beginning of the 1970‐ies carbohydrate analysis of complex natural compounds was still primitive and inaccurate. As an example, an immunological hapten, the classical Forssman hapten, a membrane‐located glycosphingolipid, was under debate whether it contained four or five monosaccharides. One reason for this was the unreliable quantitation of amino sugars.

In Gothenburg, at the Department of Medical and Physiological Chemistry (Medical Biochemistry), a young group of medical students (headed by Karl‐Anders Karlsson) was engaged in the analysis of membrane sphingolipids of human tissues, relating their composition with tissue functional characteristics, like blood group status, ion transport, tumor formation. In the same building, Einar Stenhagen, holding a foundation professorship and his own Department, had in 1968 installed a new mass spectrometer, a high resolution MS 902 double‐focusing instrument (AEI/Kratos Ltd., Manchester, UK) equipped with a standard EI source and a heatable direct‐insertion probe. This inspired attempts to improve sphingolipid, especially glycosphingolipid, tissue pattern analysis by mass spectrometry for information on lipophilic components (fatty acids and long‐chain bases) as well as linked oligosaccharides (sequence). Various derivatives of intact glycolipids were initially tested, including acetyl, trimethylsilyl and trifluoroacetyl derivatives. A highly informative picture finally emerged using permethylation, and permethylation combined with lithium aluminium hydride reduction (amide of ceramide and of N‐Acetyl sugars converted to amine, and methylester of carboxyls converted to alcohol). The reduction had earlier been used by Klaus Biemann to improve peptide volatility.

The two mass spectra of the Forsmann glycolipid hapten isolated from horse kidney (ref. 11) unambiguously established the lipid components and monosaccharides (three hexoses and two N‐acetyl hexosamines). Strong sequence peaks with expected mass shifts for amide to amine including a very abundant ion containing the fatty acid and the whole saccharide, allowed a safe conclusion on ceramide composition and saccharide sequence. The first published paper (ref. 12) was on the GM1 five‐sugar ganglioside, the receptor for cholera toxin. Soon a paper also appeared in the first issue of Biomedical Mass Spectrometry (ref. 13). The first oral presentation was at the International Congress of Biochemistry in Stockholm in 1973. After the talk, Sen‐itiroh Hakomori, later a member of the US Academy of Sciences and the most productive and successful of glycolipid scientists, rushed up from his seat to obtain all necessary information on sample handling. In the years to follow many dozens of new glycosphingolipids were characterized using this technique. The largest glycolipid successfully analyzed was a twelve‐sugar blood group A‐active compound of rat intestine (ref. 14). It may be noted that the largest biomolecule analyzed by EI mass spectrometry thus far was a six‐sugar ganglioside of human brain with molecular‐weight ions at m/e 2245 (ref. 15).

The abundant and specific reporter ions of individual glycolipids made it possible to fingerprint natural mixtures by a distillation, which was developed to sophistication using upgraded instrumentation and computer programs, as reviewed in detail (ref. 16). Thus the in‐beam technique with specially treated quartz cuvettes allowed a successive evaporation of molecular species according to size up to a temperature of more than 300 centigrades without signs of cracking. Numerous studies and doctoral theses have been reported using these techniques on glycosphingolipids in relation to blood groups and transplantation, tissue differentiation, tumor formation and as receptors for bacteria and viruses.

One may recall that Einar Stenhagen suddenly passed away in December 1973, only half‐a‐year after the death of his wife Professor Stina Stenhagen, in both cases due to late complications of tuberculosis that they acquired in their youth. Einar was excited by these early MS results on glycolipids and that a new sequence method was developed using his instrument. His visits to the glycolipid lab grew more frequent during the last autumn, and he could enjoy generous time to manually count up the peaks of new compounds appearing on the rolls of UV recordings.

Plasma desorption mass spectrometry of proteins

The work on the plasma desorption process at the Ion Physics Department in Uppsala (ref. 17) and the collaboration with P Roepstorff in applications on protein analysis is described in another chapter of this book.

1. Sarah Ratner, in “Biochemical Applications of Mass Spectrometry” (George R. Waller, ed.) Wiley‐Interscience, 1972, pp. 1‐10).

2. Ryhage R (1993) The mass spectrometry laboratory at the Karolinska Institute 1944‐1987. Mass Spectrom. Rev. 12:1‐49

3. Ryhage R, Stenhagen E (1960) Mass spectrometry in lipid research. J. Lipid Res. 1: 361‐390.

4. Stenhagen E (1972) Some early examples of the application of mass spectrometry to the elucidation of the structure of complex molecules of biological origin. In “Biochemical Applications of Mass Spectrometry” (George R. Waller, ed.) Wiley‐Interscience, 1972, pp. 11‐19.

5. James AT, Martin AJP (1952) Gas‐liquid partition chromatography: the separation and micro‐estimation of volatile fatty acids from formic acid to dodecanoic acid. Biochem J. 50:679‐690.

6. Ryhage R (1964) Use of a mass spectrometer as a detector and analyzer for effluents emerging from high temperature gas liquid chromatography columns. Anal. Chem. 36: 759‐764.

7. Stenhagen E (1964) Jetziger Stand der Massenspektrometrie in der organischen Analyse. Z. Analyt. Chem. 205: 109‐124.

8. Throck Watson J, Biemann K (1964) Direct recording of high resolution mass spectra of gas chromatographic effluents. Anal. Chem. 37: 844‐851

9. Sweeley CC, Elliott WH, Fries I, Ryhage R (1966) Mass spectrometric determination of unresolved components in gas chromatographic effluents. Anal. Chem. 38: 1549‐1553.

10. Hammar C‐G, Holmstedt B, Ryhage R (1968) Mass fragmentography: Identification of chlorpromazine and its metabolites in human blood by a new method. Anal. Biochem. 25: 532‐548.

11. K.‐A. Karlsson, H. Leffler, B.E. Samuelsson (1974) Characterization of the Forssman Glycolipid Hapten of Horse Kidney by Mass Spectrometry. J. Biol. Chem. 249: 4819‐4823.

12. K.‐A. Karlsson (1973) Carbohydrate Composition and Sequence Analysis of Cell Surface Components by Mass Spectrometry. Characterization of the Major Monosialoganglioside of Brain. FEBS Lett. 32: 317‐320.

13. K.‐A. Karlsson, I. Pascher, W. Pimlott, B.E. Samuelsson (1974) Use of Mass Spectrometry for the Carbohydrate Composition and Sequence Analysis of Glycosphingolipids. Biomed. Mass Spectrom. 1: 49‐56.

14. M.E. Breimer, G.C. Hansson, K.‐A. Karlsson, H. Leffler, W. Pimlott, B.E. Samuelsson (1981) Sequencing of Oligosaccharides by Mass Spectrometry Applied on a 12‐Sugar Glycolipid. FEBS Lett. 124: 299‐303.

15. K.‐A. Karlsson (1974) Carbohydrate Composition and Sequence Analysis of a Derivative of Brain Disialoganglioside by Mass Spectrometry, with Molecular Weight Ions at m/e 2245. Potential Use in the Specific Microanalysis of Cell Surface Components. Biochemistry 13: 3643‐3647.

16. B.E. Samuelsson, W. Pimlott, K.‐A. Karlsson (1990) Mass Spectrometry of Mixtures of Intact Glycosphingolipids.. Methods Enzymol. 193: 623‐646.

17. J. Bergquist, P. Håkansson, B. Sundqvist, R. Zubarev (2007) Mass spectrometry of proteins – Uppsala perspectives on past and present. Internat. J. Mass Spectrom. 268: 73‐82.

The Mass Spectrometry Club, the Swedish Mass Spectrometry Society and their Meetings

Prior to the formation of SMSS (the Swedish Mass Spectrometry Society), Swedish mass spectrometry research was presented as sessions at meetings of other societies.

Examples are:

1958. At a meeting of the Swedish Biochemical Society in Uppsala, June 6‐7, 1958, Bergström, Ryhage and Stenhagen reported on mass spectrometric studies of bile acids and steroids.

1963. A conference on “Biochemistry of Lipids” was held August 5‐7 at the Wennergren Center in Stockholm where the first interface between a gas chromatograph and a mass spectrometer was described by R. Ryhage.

1964. On May 14‐15, the British Biochemical Society had its 439th meeting jointly with the Swedish Biochemical Society in Stockholm on “Recent advances in separation and structural analysis”. S. Abrahamsson, S. Ställberg‐Stenhagen and E. Stenhagen discussed data acquisition and computer search of mass spectra and Ryhage and Sjövall described direct mass spectrometry of steroids in gas chromatography effluents.

1969. An EMBO Workshop in Applied Mass Spectrometry was organized by the Laboratory for Mass Spectrometry at Karolinska Institutet, April 21‐23, 1969. Professor S. Bergström made the opening remarks and speakers were K. Biemann, W. McMurray, G. Spiteller, R Ryhage, A.A. Kiryushkin, H.M. Fales, R.A. Saunders, B. Holmstedt, J. Sjövall, H. Budzikiewicz.

1973. At the 9th International Congress of Biochemistry, Stockholm 1‐7 July 1973, the section biochemistry of lipids had a session on mass spectrometry. Chairmen and speakers were: E. Lederer, E. Stenhagen, K. Biemann, H.M Fales, A.L. Burlingame, R.Ryhage, C.C. Sweeley, Topics like investigation of complex mixtures, chemical ionization, real‐time mass spectrometry, computer methods, and multiple ion detection techniques in qualitative and quantitative analyses of lipids were discussed. In other sessions, mass spectrometric applications were discussed, such as analyses of phospholipids, prostaglandins and glycosphingolipids and metabolic profiling studies using isotope‐labeled ethanols.

1974. The Analytical Section of the Swedish Chemical Society had a meeting ( “temadagar”, (theme days) on gas chromatography‐mass spectrometry, January 21‐23 in the town Skövde. The former CEO of LKB (S. Malmström) described how the first commercial GC‐MS instrument (LKB 9000) was developed. Applications of the method in a wide variety of areas were described by S. Agurell, E. Jellum, J. Sjövall, C. Enzell, C.‐G. Hammar, S. Jensen, I. Qvist, G. Widmark, E. Änggård B. Holmstedt. Integrated systems, GC‐MS‐computer acquisition and evaluation of spectra were subjects of a panel discussion.

1983‐1985: At the 5th Nordic Mass Spectrometry Conference in Finland 1983 it was decided that the next meeting should be held in Sweden and when the 6th Nordic Conference was to be arranged in Sweden in 1986 there was a need for an organizing committee. Upon the initiative of Birgitta Sjöquist and Jan Sjövall, a Swedish Mass Spectrometry Club was started within the Analytical Section of the Swedish Chemical Society. A steering committee was formed consisting of Gunnar Bergström, Ingemar Björkhem (representing the Board of the Analytical Section of the Swedish Chemical Society), Curt Enzell, Bengt Karlsson (the Swedish Chemical Society), Birgitta Sjöqvist and Jan Sjövall. They held their first meeting February 18, 1985. The first arrangement of the MS‐Club was decided to be a work‐shop in Stockholm on November 8, 1985 at “Allhuset”, Stockholm University. A mini‐symposium “Soft ionization methods and LC/MS” was arranged and attracted about 150 participants. Lectures were given by M. Vestal (thermospray LC/MS), P. Roepstorff (comparison of FAB and plasma desorption MS of peptides), and P. Arpino (evaluation of LC‐MS relative to GC‐MS). A panel discussion was held on soft ionization methods and comparisons of LC‐MS and GCMS. The panel consisted of the speakers, G. Bergström, C. Enzell, S Marklund, B. Samuelsson, B Sjöqvist, J. Sjövall, G. Stenhagen, S. Svensson.

1986: The 6th Nordic Mass Spectrometry Conference was held on May 25‐28 at Borgholm, Öland, Sweden. It was organized by the steering committee of the MS‐Club and attracted about 150 participants. Plenary lectures were given by B. Sundqvist (molecular ion formation by particle impact), W. Francke (GC/MS and insect chemistry), T. Baillie (mass spectrometric studies of pathways of drug metabolism), C. Fenselau (middle molecule mass spectrometry: 3000‐16000 Daltons), K. Rinehart, Jr. (applications of FAB‐MS and LC/FAB‐MS, to biologically active compounds), K. Nakanishi (MS studies of some bioactive compounds). One session concerned GC‐MS analysis of chlorinated dibenzodioxins and dibenzofurans in environmental samples. Other sessions dealt with analyses by LC‐MS, plasma desorption MS, fragmentation chemistry and hydrogen exchange. On the program was an excursion to Uppsala University Ecology Plant Station on Öland with Gunnar Bergström as guide. At this station the first prototype of the first commercial GC/MS instrument (LKB 9000) was used in studies of pheromones by Stina Ställberg‐Stenhagen. It had previously been used in the laboratories of Bergström, Samuelsson and Sjövall at Karolinska Institutet in studies of prostaglandins, bile acids and hormonal steroids. The Technical Museum in Stockholm was not interested in this instrument which was discarded in 1980. A second prototype went to George Waller, Oklahoma State University, and was later donated to and accepted by a Smithsonian museum.

1987: “Analysdagarna” (the Analytical Days of the Chemical Society) were held in Lund, June 9‐12. One of the minisymposia at this meeting was arranged by the MS‐Club.

1988: April 26, the Royal School of Technology, Stockholm. The first Annual Meeting of the MS‐Club was celebrated by organizing a “theme day” held in cooperation with the Analytical Section, with the following speakers: D.E. Games and S. Evans presented SFC/MS and SF/MSMS. C.J.W. Brooks talked about functional group derivatives in GC/MS. I. Kamensky gave a lecture on plasma desorption mass‐spectrometry ‐ an analytical tool in protein chemistry. Representatives of VG‐Analytical, Kratos, Bio‐Ion Nordic AB and Nermag presented instrumental news. At this first Annual Meeting G. Bergström and C. Rappe were elected as board members for one year and C. Enzell and J. Sjövall for two years.

1989: At the Annual Meeting Nico Nibbering, Amsterdam, gave a lecture on analytical applications FTICR Mass Spectrometry. Sjövall and Enzell represented the MS‐Club at the 7th Nordic Mass Spectrometry Conference. A day in mass spectrometry was arranged in Umeå on May 30. Sjövall was the Swedish representative at the International Committee for the 12th International Mass Spectrometry Conference. G. Bergström and C. Rappe were reelected for the board of the MS‐Club.

1990: The Annual Meeting was held March 5‐6 in Gothenburg and dealt with mass spectrometry of larger molecules. Lectures on plasma desorption and MS‐MS were given by B. Sundqvist, P. Roepstorff, P. Derrick, D. Wood and I. Szabo. The Gothenburg group (G. Hansson, J. Holgersson, H. Karlsson, K.‐A. Karlsson, B. Lanne, B. Samuelsson, S. Teneberg) presented their data on mass spectrometry of glycosphingolipids and oligosaccharides. G. Stenhagen described microcolumn LC/MS in the EI mode with data acquisition using a PC. At the board meeting of the MS‐Club on May 17 it was decided that the MS‐Club should form a separate section within the Swedish Chemical Society. This was agreed on September 12 when representatives of the boards of the MS‐Club and the Analytical Section met. C. Enzell and J. Sjövall were re‐elected for two years.

1991: The Annual Meeting was held on February 14 at Stockholm University. Lennart Kenne and Per‐Erik Jansson gave a lecture on “Mass spectrometry and structural analysis of carbohydrates.” Yngve Zebühr lectured on “Analysis of dioxins in environmental samples”. Karin Markides was elected a member of the board, which now consisted of five people. The MS‐Club got its new rules as a section within the Swedish Chemical Society. A spring meeting, “Liquid chromatography/mass spectrometry‐current status and future trends” was arranged by Claes Lindberg, Draco, in Lund, April 11‐12 with 120 participants One of the invited speakers was Jan van der Greef..A fall meeting of the Swedish MS‐Club was arranged by Bo Sundqvist in Uppsala, November 18‐19.

1992: The Annual Meeting was held on May 25 at the office of the Swedish Chemical Society.

1993: The Annual Meeting was held on April 22 at Kabi Pharmacia, Stockholm, whose mass spectrometric activities were presented. The board of the MS‐Club now consisted of: Claes Lindberg (new member), Karin Markides, Bengt Norén (new member), Bo Samuelsson (new member) and Jan Sjövall. On April 29, Fred McLafferty gave a talk on “High resolution mass spectrometryof large biomolecules” and Howard Morris gave a talk on “Mass spectrometry in glycobiology and biotechnology” at the Department of medical chemistry, Karolinska Institutet. A fall meeting on “Biomedical Applications of Mass Spectrometry” was arranged by Kabi Pharmacia in November. The formation of a European Mass Spectrometry Society was announced.

1994: The Annual Meeting was held on April 14 at Nobel Forum, Karolinska Institutet. Leif Bertilsson and Carl‐Axel Nilsson were elected new members of the board succeeding C. Enzell and K. Markides. Jan Sjövall resigned as chairman of the board and was succeeded by Bo Samuelsson. Sjövall was appointed honorary member of the board. The Club introduced an annual membership fee of 30 SEK. Bengt Norén represented the MS‐Club at the ESMS and IMSC meetings.

1995: The Annual Meeting was held on April 5 in Gothenburg in connection with the meeting “KEMI 95”. The Club contributed with a session on “new mass spectrometric techniques for larger biomolecules” with lectures on instrument development from Finnegan‐MAT, VG Analytical, Bruker, and PE SCIEX.

A Symposium ”Impact of Biomedical Mass Spectrometry” in the series “Frontiers in Medicine” at Nobel Forum was arranged by Karolinska Institutet and held on September 18. A number of prominent speakers participated: A.L. Burlingame, R.D. Smith, B.T. Chait, D. Hunt, R. Aebersold, C.H.L. Shackleton, B. Sundqvist, P. Roepstorff, M. Mann, K.‐A. Karlsson, R.C. Murphy, and J. Sjövall. Emphasis was on characterization of proteins and their interactions with large and small molecules, sequencing of glycolipids, lipid mediator biochemistry, steroids and bile acids in clinical contexts.

1996: The Annual Meeting was held on January 23 at the department of medical and physiological chemistry in Gothenburg when D.M. Desiderio gave the lecture “The use of mass spectrometry for the analysis of opioid peptides and proteins in the human”. The MSClub arranged a mini symposium in Lund on “mass spectrometry in biomedical research” within the meeting of the Analytical Section (Analysdagarna) in Stockholm and together with the Swedish Academy of Pharmaceutical Sciences “Mass spectrometry in pharmaceutical research and development”

1997: The Annual Meeting was held on April 14, at Huddinge Hospital, Stockholm. The scientific program dealt with drug analysis. The EUCHEM‐Conference: Mass Spectrometry in Biology, initiated by Bo Samuelsson and the MS‐Club was held at Hindås June 7‐12. The Conference was held at Hjortviken in Hindås some 30 km east of Gothenburg surrounded by forest and close to the beautiful lake Västra Nedsjön. The idea was to discuss mass spectrometry in a secluded, calm place, inside in the lecture hall and outside in the forest at the fireplace or canoeing on the lake.

Through The Royal Swedish Academy of Sciences, The Swedish National Committee for Chemistry and The Swedish Chemical Society a reasonable amount of money was allocated to invite leading researchers from all over the world.

The theme was chosen to diminish the gap between researchers dealing mainly with instrumental development and technique and researchers dealing mainly with the biological problems and to promote creative discussions between them. For this purpose not only mass spectrometrists were invited but also some scientists in the forefront of biology. Another “trick” to “ignite” creative discussions was when inviting also to send preformed lecture titles, which deliberately had been switched between selected persons. This caused some initial turbulence, but turned out to be highly effective for the creativity and discussions. In the end many thought this created an inspiring climate.

For obvious reasons ample of time was allotted for discussions and the conference was terminated with an open discussion, “After the genome”, introduced by Peter Roepstorff and Brigitte Wittman‐Liebold and moderated by Bo Samuelsson. The heat was really on. The conference attracted some 70 delegates.

Program in short:
Introduction: Bo E Samuelsson, Fred W. McLafferty
Analysis of DNA (Gunnar C. Hansson chair): James A. McCloskey, Ken Welsh, Frans Hillenkamp, Brigitte Wittman‐Liebold, Urban Skogsberg, Detlev Suckau (Bruker Spectrospinn)
Analysis of Proteins and Peptides (Rolf Ekman chair): Peter Roepstorff, Andrew G. Ewing, Marita Larsson, Klaus Schneider, David Fenyo, Gitte Neubauer, Bob Galvin (Perkin Elmer)
Analysis of Proteins and Peptides (Jan Sjövall chair): Donald Hunt, Klas Kärre, Randall W. Nelson, Sven R. Carlsson, Östen Jansson, Carol Nilsson, William Griffiths, Yang Yang, Alma L. Burlingame, Susann Teneberg, Gunnar C. Hansson, Bob Bordoly (Micromass)
Analysis of Carbohydrates (Bo Samuelsson chair): Vernon N. Reinold, Gerald W. Hart, Catherine E. Costello, Karl‐Anders Karlsson, Niclas Karlsson, Halina Miller‐Podraza, Brian Musselman (Kebo Lab/PerCeptive Biosystems)
The conference was organized by the following committee: Rolf Ekman, Mölndal Hospital, Gunnar C. Hansson, Gothenburg University, Klas Kärre, Karolinska Institutet, Claes Lindberg, Astra Draco, Bengt Nordén, Pharmacia & Upjohn, Peter Roepstorff, University of Odense, Bo E Samuelsson, Chairman, Sahlgrenska University Hospital, Agneta Sjögren, The Swedish National Committee for Chemistry and Jan Sjövall, Karolinska Institutet.

1998: The Annual Meeting was held on April 23 in connection with “KemiStämman” in Gothenburg. Karin Markides and Gunnar Hansson were elected for the board succeeding L. Bertilsson and B. Samuelsson. The Club arranged a session “Mass spectrometry ‐ not only for specialists”. The major activity, the 10th Nordic Conference on Mass Spectrometry took place in Umeå, August 22‐25, organized by groups in Umeå and chaired by Carl‐Axel Nilsson. It had 187 participants and 33 posters. The meeting was preceeded by a two and a half day workshop for PhD students, covering LC‐MS, electrospray, GC‐MS, high resolution with labelled reference substances, MS/MS, FAB, capillary electrophoresis). Plenary lecturers were: J. van der Greef (impact of new electromigration techniques in bio‐pharmaceutical LC/MS and CE/MS), P. Roepstorff (the impact of mass spectrometry on biochemistry and molecular biology), B. Nilsson (analysis of protein glycosylation by mass spectrometry), H‐R. Buser (analysis of persistent organic pollutants by various GC/MS techniques), M. Garle (the capability to detect doping agents with mass spectrometry). Key lectures were given by P. Andrén (endogenous metabolism and release of neuropeptides using in vivo microdialysis and nanoflow electrospray mass spectrometry), P. Håkansson (the Uppsala FTICR facility), O. Dahlman (MALDI‐TOF‐MS analysis of wood derived oligo‐ and polysaccharides), M. Törnqvist (leakage of acrylamides in tunnel construction work monitored by GC‐MS/MS of protein adducts in humans and animals), G. Hallström (LC‐EC/MS/MS). Papers were presented on MS of peptides, LC/MS, cytokinins, glycolipids, neurosteroids, chlorinated pollutants and other topics.

1999: The Annual Meeting was held on April 8 in Samuelssonsalen, the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. Keith Jennings held a lecture “A study of the structure and function of selected peptides and proteins by means of ESI mass spectrometry”. The MS‐Club changed its name to the Swedish Society for Mass Spectrometry (SMSS). The Annual Meeting supported the membership of SMSS in IMSS. A website for SMSS was initiated. K. Markides succeeded B. Samuelsson as chairman of the board. She was appointed representative for the 15th International MS Conference. A decision was taken to provide support for PhD students to participate in Nordic and international conferences.

2000: The Annual Meeting was held on March 2 at Astra Zeneca R&D in Lund with lectures by Jonas Bergquist “Microseparation techniques coupled to mass spectrometry – Breaking new frontiers in neuroscience”, György Marco‐Varga, “The beauty of silicon micromachined chips in MALDI‐TOF MS” and Ole Nörregaard Jensen “Characterization of phosphoproteins by mass spectrometry ‐ Advances and challenges”. During the meeting “Nordic Lab Xpo” two mini symposia were arranged: “Mass spectrometry – not only for specialists” and “Mass spectrometry in the time following the human genome”.

2001: The Annual Meeting was held on February 23 at Analytical Chemistry in Uppsala. The SMSS board proposed to allow members of another Society (e.g. the Swedish Society of Medicine, the Swedish Society of Toxicology, the Swedish Academy of Pharmaceutical Sciences, the Swedish Society of Clinical Pharmacology, the Swedish Society for Biochemistry and Molecular Biology) to become members of SMSS at the low membership fee applicable to members of the Swedish Chemical Society. This was later approved by the Swedish Chemical Society. The “Analytical Days” had its focus on mass spectrometry since Fred McLafferty was awarded the Torbern Bergman medal by the Swedish Chemical Society. Jan Paulson was elected to the board succeeding C. Lindberg.

2002: The Annual Meeting was held on June 12‐13 in connection with the meeting “KemiForum” at Stockholm University. SMSS arranged a minisymposium at KemiForum “Strategic uses of derivatization in MS” and in cooperation with the Swedish Society for Biochemistry and Molecular Biology (SFBM), SMSS arranged a mini symposium “Mass spectrometry in molecular biology”. The Swedish Academy of Pharmaceutical Sciences and SFBM were positive to the proposal of external memberships in SMSS and a collaboration of SMSS with SFBM and the Swedish Proteomic Society (SPS) (a focus group within the Swedish Academy of Pharmaceutical Sciences) was initiated.

2003: The Annual Meeting was held on June 13 at Chalmers in Gothenburg in connection with the Analytical Days in Gothenburg June 10‐13. A session on mass spectrometry was arranged with emphasis on metabolomics and metabonomics in research on animals and plants. Speakers were: L. Sumner, T. Moritz, J. Greter, M. Landergren, H. Björkman, and O. Kvalheim.

2004: Due to competition by other meetings in the chemical field, the Annual Meeting and a planned symposium were postponed until 2005. Cooperation with SPS was discussed.

2005: The Annual Meeting was held on February 9 in the Beijer Hall at the Royal Academy of Sciences, Stockholm. A Symposium “Utilizing the Full Potential of Mass Spectrometry” was given. Among the topics were metabonomics, MS‐data collection and data handling, electrospray ionization of biomolecular complexes, proteomics data security. Lecturers were: K. Benkestock, G. Stenhagen, S. Jacobsson, H. Idborg, A. Tjernberg, J. Lengqvist, J. Nordin, D. Bylund, and G. Marco‐Varga. T. Moritz was elected to the board succeeding J. Paulson.

2006: The Annual Meeting was held on March 27 in Stockholm. J. Bergquist, L. Ilag, and P. Önnerfjord replaced B. Norén, C. Nilsson and K. Markides as board members. A Symposium “Promising developments in mass spectrometry” was held. Lectures were given by G. Cooks, G. Baykut, A. Makarov, R. Zubarev and J. Bergquist with emphasis on instrument development, particularly LTQ Orbitrap hybrid mass spectrometry, proteomics and DESI. SMSS also arranged a minisymposium “Bringing mass spectrometry into reality” at the Analytical Days in Gothenburg, June 13.

2007: The Annual Meeting was held on March 26 in Stockholm. C. Åstot was elected to the board succeeding T. Moritz. The theme of the lectures was “Mass spectrometry and structural analysis” Carol Robinson was invited as the international lecturer. About 50 people participated.

2008: The Annual Meeting was held on April 7 in Stockholm. The symposium theme was “Post‐translational modifications – challenges for academia and biotech industry”. Lecturers were: G.W. Hart, O. Nörregård Jensen, B. Lanne, J. Peter‐Katalinic, P. Önnerfjord, N.G. Karlsson, M. Hornshaw, M. Opperman, M. McDowell.

2009: The Annual Meeting was held on March 23 in Nobel Forum, Karolinska Institutet. The symposium theme was “Mass spectrometry for imaging”. Lecturers were: A. Ewing, G. Corthals, R. Caprioli, P. Sjövall. A. Nilsson, M. Opperman, D.A. Simmons. M. Becker.

2010: SMSS arranged the 14th Nordic MS Conference in Uppsala, August 18‐20. The program sessions were: “MS in protein drug characterization” with lectures by M. Wuhrer and E. Lundanes; “Technical issues and applications”, two sessions by instrument companies; “Historical developments in MS” with a lecture by Fred McLafferty; “MS in space and outer frontiers” with lecture by N. Hertkorn; “MS against war, crime and terror”; “Quantitative MS in system biology” with lectures by J.V. Olsen and M. Mann; “New developments in fundamental MS”, two sessions including lectures by R Kostiainen and F McLafferty. There were few representatives from the other Nordic countries which resulted in discussions of a closer collaboration between the Nordic countries. The Annual Meeting was held on August 20 in Uppsala. It was decided that the board should consist of seven members and consequently the two deputy members were elected members of the board. Thus the board consisted of Gunnar Hansson, Gothenburg, chairman, Jonas Bergquist, Uppsala, Leopold Ilag, Stockholm, Niclas Karlsson, Gothenburg (newly elected), Elke Schweda, Stockholm, Roman Zubarev, Stockholm, Patrik Önnerfjord, Lund, and Jan Sjövall (honorary member). SMSS also arranged a minisymposium at “the Analytical Days” in June, in Uppsala.

Teaching mass spectrometry

The board of SMSS has discussed the possibility of organising teaching courses in mass spectrometry but has decided to leave this task to Departments at individual Universities and industry. In this way many courses dealing with different aspects of mass spectrometry have been available to PhD students. An example of the immediate benefit from such a course was the discovery of PCBs in extracts of animal tissues. One of the students, Sören Jensen, was analyzing DDT and its metabolites in lipid extracts from fish and sea‐eagle by GLC with electron capture detection. A series of up to 14 peaks of unknown origin was found in the chromatograms. When participating in a course on GLC and GC/MS organised by Sjövall and Ryhage in 1966, Jensen was given the opportunity to analyze his extracts by GC/MS. He could interpret the spectra and drew the conclusion that the unknown peaks were due to polychlorinated biphenyls (PCBs). This started a new era in chemical environmental analysis and eventually (1972) the use of PCB was banned in Sweden and finally in 1995 it was totally forbidden by law. Jensen´s discovery led to the establishment of several laboratories in Sweden analyzing halogenated persistant pollutants, notably one in Umeå led by C. Rappe, one at Karolinska Institutet led by K. Norén focused on mother´s milk and one at the Department of Environmental Chemistry at the Wallenberg laboratory, Stockholm University. The number of known persistent halogenated pollutants is now overwhelming.

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