Bioinformatics in Switzerland From BIONET to SIB 1984-2000

Bioinformatics in Switzerland

From BIONET to SIB1984-2000

Swiss-Prot 20th anniversaryFortaleza, Brazil

Obscurantism, Swiss style

Biology students are forbidden to take computer science courses (CVJ, circa 1970, Manuel Peitsch, circa 1980)

Sequence analysis is not considered to be an acceptable study area for a PhD (Philipp Bucher, circa 1980)

A well-known Swiss scientist claims that he can find patterns and restriction sites in a sequence faster by eye than with a computer (circa 1985)


But in the meantime…

Amos Bairoch teaches himself computer science, and convinces his boss (Robin Offord) that bioinformatics is a legitimate field of study

Philipp Bucher gets trained in sequence analysis with Ed Trifonov (Weizmann Inst) and Sam Karlin (Stanford)

CVJ learns basic computer science at UNC Chapel Hill and UC San Francisco

Ron Appel gets his education as a computer scientist in Geneva

Manuel Peitsch gets trained in molecular modeling with Jacob Maizel (NCI, Frederick)


Beginnings

1982: Amos starts BIONET, a group of hackers, biologists and software pirates in Geneva and Lausanne

1983: Staden package installed for ISREC on a computer at EPFL

1983-4: microcomputers (Sirius/Victor) find their way into some biology labs in Switzerland

1984: first release of the ancestor of PC-Gene 1984: Manuel Peitsch (undergraduate) starts

developing software on a microcomputer at ISREC


Problem #1: infrastructure

Obscurantism redux: biologists do not need mainframe computers!

Real issues: Enough storage for local copies of sequence databases Enough CPU power and memory to search through

databases (FASTA, then BLAST) Robust software suite for sequence analysis (GCG,

Intelligenetics, Staden, etc) Administrator level access for software maintenance,

database updates, etc. 1984-2003: constant battle to have access to

sufficient computing resources


Infrastructure – a continuing saga

1984-1998: repeatedly rejected attempts to use the computer center of the U. of Lausanne

1985-1988: access to the computer and software of the Friedrich Miescher Inst. (Basel), but at a cost!

1989-2003: series of agreements and collaborations with a.o. The Swiss EMBnet node in Basel Epidemiologists at the Medical Faculty Pharmacists at the Natural Science Faculty The Swiss National Scientific Computing Centre The Ludwig Institute for Cancer Research

2003: inauguration of the Vital-IT Centre, HPC facility dedicated to life science research


Nucleotide sequence databases

Distribution of data was a real issue – had to rely on 9 mm tapes, and later CDs sent by post from Heidelberg

Swiss EMBnet node (1988, Reinhard Doelz, Basel) created distribution mechanism (HASSLE, FTP), but international network bandwidth remained a major problem

Proper mirroring of databases has become “easy” only thanks to the evolution of the Internet into a well-connected, high-speed network


Personalities and achievements

Switzerland has been lucky to be home to a few scientists and politicians with a real vision and commitment to bioinformatics

… and apologies to those I may have forgotten


Milestones in Swiss bioinformatics - 1

1986: Swiss-Prot 1.0 !!! 1988: founding of Swiss EMBnet node, run

by Reinhard Doelz (Basel) Development of HASSLE protocol, incorporating

many features of modern Grid computing 1989: collaboration between Ron Appel and

Amos Bairoch creates a bioinformatics center focussed on proteomics



1990: creation of a bioinformatics group at ISREC Philipp Bucher, with primary interest in

the analysis of promoters (EPD) and of sequence motifs

Roland Luethy, with primary interest in the analysis of sequence-structure relationships



1991: first version of Swiss-Model, an automated server for producing 3D models (Manuel Peitsch)

1991: The first Entrez client outside the US is installed in Lausanne (Manuel Peitsch)

1993: ExPASy goes live as the first Web server dedicated to life sciences Among first servers offering database search services Among first applications of “push” technology (Swiss-

Shop) Integration and “portal” concept at the core of the server



1992: Gaston Gonnet and Steven Benner use the “all against all” protein sequence comparison approach to derive novel substitution matrices

1993: Swiss-2DPAGE pioneers the concept of providing a common framework for federating data from multiple sources (Ron Appel)

1996: First version of Swiss.PdbViewer, a public domain 3D viewer and modelling environment (Nicolas Guex)

1997: MOLLUSCS, an early implementation of distributed sequence database searches on a Linux PC cluster (Thomas Junier, Christian Iseli)

1998: 3D-Crunch, an effort to produce genome-scale high-quality protein structure models (Nicolas Guex, Manuel Peitsch)


Switzerland and the EBI

Bernhard Hirt was Chairman of the EMBL Council during the period when EBI was conceived and created (1991-1994) Developing the concept Outlining funding model (problems with EC!) Selection of the site: Hinxton, because of superior Internet

connectivity! Paolo Zanella (U. of Geneva & CERN) first Director Collaboration with SWISS-PROT at center of EBI

database group activities Amos Bairoch and Klaus Müller members of the

Advisory Board defining initial EBI activities


The rocky road to SIB

A series of funding crises 1991: both EMBnet.ch and Swiss-Prot try to get support for their activities

– Swiss-Prot receives some funding from SNF 1996: EMBnet.ch in Basel throws in the towel, Swiss-Prot fails to receive

expected EC funding – international outcry 1996-2000: BandAid solutions keep services going, Swiss-Prot goes

commercial A series of initiatives

Push from Swiss Govt to merge service activities with existing Academies or to create a fundable institution

Trying to create a consensus within and between the Universities of Lausanne and Geneva

Birth of an institution 30 March 1998: the Geneva Cantonal Govt sponsors the creation of a

new non-profit Foundation, the SIB 15 May 1998: first meeting of the SIB Foundation Council

1 Jan 2000: Federal funding starts


Behind the scenes - Geneva

Robin Offord (Professor, Biochemistry) Supported Amos and his work through many difficult times Was instrumental in lobbying the Government for

resources and support Denis Hochstrasser (Professor, Hospital Labs)

Gave the impetus for the development of proteomics Major force in founding SIB, Genebio, Geneprot

Guy-Olivier Segond (politician) Realized the importance of bioinformatics for the

development of Geneva Forced Universities and political authorities to create SIB


Behind the scenes - Lausanne

Bernhard Hirt (Director, ISREC) Supported development of bioinformatics at ISREC and

University of Lausanne Provided help for Swiss-Prot during several crises Chairman of EMBL Council, instrumental in creating and

siting EBI Lloyd Old (Director, Ludwig Inst. Worldwide)

Provided generous support to start the SIB groups in Lausanne

Daniel Mange (Professor of Computer Science) Realized importance of biological models for computer

science (bio-inspired computing)


Behind the scenes - Basel

Thomas Bickle (Professor, Biozentrum) Obtained support and funding for first Swiss EMBnet node Participated in creation of bioinformatics groups

Gian-Reto Plattner (Professor of Physics and Senator) Obtained funding and support for bioinformatics at

University of Basel Member of the SIB Executive Board

Joachim Seelig (Director, Biozentrum) Ensured support from the Swiss National Fund

Andreas Engel (Professor, Biozentrum) Oversaw development of bioinformatics at Biozentrum


Behind the scenes - more

Charles Kleiber, Secretary of State for Education and Research

Jean-Raoul Scherrer (Geneva University Hospital)

Christian Pellegrini (U. of Geneva) Paul Herrling (Novartis) Jonathan Knowles (Glaxo, Roche)


Lessons learned from SIB

A bottom-up approach often works better than top-down Scientists working together can accomplish more than

ministries handing down decisions Funding is important, but cannot replace

enthousiasm and commitment Much of the landmark work performed by current SIB

group leaders was done “outside of working hours” and not specifically funded

A well-funded Institute needs professional management It is not enough to do good science and provide efficient

services, you have to produce the documents that prove it


Ron AppelAmos BairochPhilipp BucherManuel PeitschVictor Jongeneel

Nicolas GuexTorsten SchwedeMike PrimigCédric Notredame

Mauro DelorenziOlivier MichielinBastien ChopardErik van NimwegenMihaela Zavolan

Marc Robinson-RechaviSven BergmannEvgeni ZdobnovBernard MoretJoerg StellingGaston Gonnet

Ernest Feytmans

Documents

Bioinformatics in Switzerland From BIONET to SIB 1984-2000