Sanger Institute history

John Sulston’s original grant proposal.

John Sulston’s original grant proposal. [John Sulston]

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Fewer than 50 people were employed when the Sanger Institute, then called the Sanger Centre, was officially opened on 4 October 1993; today more than 800 people work here. Alongside us on the Genome Campus is the European Bioinformatics Institute, with more than 300 staff. With a vision to provide world-class research on a large scale, we have evolved from principally a sequencing centre to a leader in biomedical research. Set on this path by John Sulston, founding Director, the Institute grew and matured under our previous Director, Allen Bradley, to seize the opportunities offered by new technologies and new understanding in genetics. The Institute's current Director, Mike Stratton, leads the Institute as it enters a new era of genome research - an era that will be about translating the research efforts of the past decade to develop new treatments for the patients of the future.

Birth: search for a home (1992-1993)

In 1992 the Wellcome Trust and the UK Medical Research Council agreed to fund a new research centre that would play a role in mapping, sequencing and decoding the human genome and the genomes of other organisms. The decision by the European Molecular Biology Laboratory (EMBL) to site its outstation, the European Bioinformatics Institute (EBI) in the UK helped to secure the decision. The new institution was to be called the Sanger Centre after Fred Sanger, the double Nobel Prize-winning biochemist, whose techniques of DNA sequencing would power it. John Sulston was chosen, apparently to his own "astonishment", as the Sanger Centre's Director.

Fred Sanger officially opened the Sanger Centre on 4 October 1993.

After searching various locations around the UK, John and his colleagues chose an estate adjoining the small village of Hinxton as the site for the project. In the early months of 1993, a handful of staff moved onto the site and got to work, sequencing genomes in temporary labs at Hinxton Hall, nine miles south of Cambridge. By March 1994, 130 people were working to uncover the genetic basis of humans.

One of the earliest realisations was that a robust IT architecture would be needed to support the ambitious aims. It was widely appreciated that the six workstations and a dozen or so terminals in place at the beginning would not be enough.

The early years: small creatures (1993-1998)

John Sulston built a Board of Management with researchers Alan Coulson, Jane Rogers, Richard Durbin, David Bentley, Bart Barrell and Murray Cairns, the Institute's Secretary. These seven led the Institute in its primary aim: to build the expertise and systems to help to complete the Human Genome Project.

We sequenced the first animal genome, the nematode worm, with collaborators at Washington University in St. Louis.

The Sanger Institute's first five-year plan, published in 1995, proposed the ambitious goals of completing the genomes of two yeasts, the nematode worm and at least one-sixth of the human genome.

The organisms simpler than the human were models for the assault on the human genome. The yeast Saccharomyces cerevisiae, with a genome of 12 million bases, was the first to fall in 1996; the nematode worm Caenorhabditis elegans, which, at 100 million bases, was the first animal and largest sequenced genome, followed in 1998.

From the early days, Institute staff shared their work with lay audiences.

From the early days, Institute staff shared their work with lay audiences. [Genome Research Limited]

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Although 1996 and 1998 mark the completion of these sequences, much of the data generated in these projects was made available prior to completion. From its earliest days, the Sanger Institute placed sequence information in the public domain as swiftly as possible, arguing that was the best way to speed research.

Work on the yeast, in particular, led to new programmes at the Institute in pathogen genomics. Mycobacterium tuberculosis was the first pathogen genome sequenced at the Sanger Institute and completed in 1998.

By the end of 1997, 36 million bases of human DNA sequence alone were emerging each year, up from 0.1 million in the Institute's first year. Just over 300 staff were connected on an IT network supporting almost 500 devices.

In its first five years to 1998, the Sanger Centre ramped up output of DNA sequence 100-fold. For the assault on the human genome, the Institute scaled-up its operation even further. In 1998, the Institute, supported by the Wellcome Trust, successfully bid to contribute one-third, rather than one-sixth, of the human genome. It had already produced 90 million bases of sequence, but would need to produce ten times more - 900 million bases - to meet that commitment.

Youthful discovery: our genome and other animal genomes (1998-2003)

The bargain to increase output was met, and the Institute led the research on the first human chromosome ever sequenced, chromosome 22, in December 1999. In a series of tumultuous events that garnered enormous interest, the human draft genome sequence was produced in June 2000 and the Human Genome Project reached its goals in April 2003. The Sanger Centre made the largest single contribution.

We now produce more sequence in one hour than we did in our first ten years.

With the draft sequence to hand, John Sulston stepped down as Sanger Centre Director, encouraging the search for a successor who would wrest biological information from genomes and build biology and genetics on the Centre's foundation in sequencing. In Allan Bradley, the Institute found just such a leader.

Confocal of C. elegans.

Confocal of C. elegans. [Dr David Becker, Wellcome Images]

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The Sanger Institute made the largest single contribution to the gold standard human genome sequence.

Allan sought to move the Institute's research into understanding gene function on a genome-wide scale; however, he wanted that move to be led by researchers who had burning questions they sought to answer, researchers whose questions could be answered only using the skills in large-scale research found at the Institute.

That Faculty of researchers has driven the new enquiries and projects that have been established at the Institute, breaking new ground in the discovery of genome landscapes.

To reflect more closely the size of the institution and its role within the Wellcome Trust's portfolio of research, in 2001, the alliterative Sanger Centre gave way to the more structured Wellcome Trust Sanger Institute.

Growing maturity: decisions and responsibilities (2003-2010)

The final steps of the Human Genome Project were taken in 2004 and 2006, as the last scientific publications appeared: the summary of the genome and the sequence of the largest human chromosome. The first and the last scientific papers for the Project were led by the Sanger Institute.

The research programmes deployed under Allan Bradley's Directorship broadened the work of the Institute: in 2000, perhaps 80 per cent of the Institute staff worked on genome sequencing and mapping; by 2004 that figure was around 20-30 per cent. New young researchers, the lifeblood of any institution, were attracted as the new Faculty recruited a larger number of postdoctoral fellows and the Institute enhanced its graduate student programme. All students are registered at the University of Cambridge.

The Institute remained a leader or major partner in large, national or international programmes such as the International HapMap Project, studying human variation; the Copy Number Variation Project, studying structural changes in human genomes; the Wellcome Trust Case Control Consortium, studying genetic association with common disease; and the KOMP and EUCOMM programmes, generating mouse mutant resources.

DNA sequence is becoming a scaffold for biology.

DNA sequence is becoming a scaffold for biology. [Genome Research Limited]

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To capitalise on these new opportunities, in 2006 the Institute focused its research efforts on those areas of biomedical research to which it could make the greatest unique contribution. Its programme of global studies of natural variation and experimental variation of genome sequence is intended to deliver data and biological resources that will prime research across the globe. The Institute's work will advance the efforts of scientists to tackle human disease, in the same way that the Human Genome Project had stimulated discovery of genes implicated in human disease.

Although the Institute's focus is in the genetics of human, mouse, zebrafish and pathogens, improvements in sequencing technology mean that the Institute can now produce more DNA sequence in one hour than it did in the ten years from its founding to the end of 2002. With the efforts of the Sanger Institute and many others, DNA sequence is becoming the scaffold for biology that it should be, the support that allows research into human biology and human disease to proceed unfettered by limited access to this most fundamental of codes.

In March 2010 Professor Leena Peltonen, a leading geneticist and head of Human Genetics at the Institute, died after a long illness. Her impact continues to be felt through the strengthening and developing of Human Genetics at the Institute. [Read obituary]

In April 2010 Professor Allan Bradley stepped down as Director to devote time to the development of a promising novel technology in mouse genetics. Allan's vision reshaped the Institute's scientific portfolio: he transformed the Sanger Institute from a world leading sequencing centre to encompass groundbreaking research into the impact of genetics on health and disease. Allan assumed the new title of Director Emeritus. Professor Mike Stratton, head of the Institute's Cancer Genome Project, was appointed Director.

* quick link - http://q.sanger.ac.uk/u3xji9ak