Matches in SemOpenAlex for { <https://semopenalex.org/work/W2014666135> ?p ?o ?g. }
Showing items 1 to 56 of
56
with 100 items per page.
- W2014666135 abstract "John SulstonJohn Sulston, one of the key international players in the human genome project, has recently published his account and recollections of the events that unfolded in the pursuit of this landmark goal. c reports.Fig. 1Public triumph: geneticist John Sulston led a major international component of the publicly funded human genome project based at the Genome Campus, at Hinxton, near Cambridge, UK. Photograph: The Wellcome Trust.View Large Image | View Hi-Res Image | Download PowerPoint Slide‘I remember standing with Bob Horvitz at the window of the old lecture room a year or so after we moved to Hinxton, looking at the enormous hole in the ground that was to be our new building. “John,” he asked me, “do you really know what you are doing?”'1Thus Sulston recalls one moment in the huge shift from being a researcher on the genetics and development of the worm Caenorhabditis elegans at the MRC Laboratory of Molecular Biology in Cambridge to director of one of the biggest gene sequencing labs in the world. ‘Some of my oldest colleagues and friends could not hide their astonishment that I should have ended up in this position,’ he writes. Britain was set to be a major player in the goal of sequencing the human genome with funding from the Wellcome trust and Sulston was to be in charge. His book111The Common Thread, by John Sulston and Georgina Ferry. Published by Bantam Press. ISBN: 0593 048016 written with author Georgina Ferry, gives his account of this extraordinary project.Sulston looks to the first musing about such an audacious project. In 1984, molecular biologist Robert Sinsheimer at the University of California at Santa Cruz, began to wonder why the large sums of money involved in major telescope projects should not be raised for biology. He wondered if there were scientific opportunities that were being overlooked, simply because we were not thinking on an adequate scale.Sinsheimer thought about developing a genome sequencing institute at Santa Cruz and convened a meeting of around a dozen scientists with expertise in DNA mapping, automated sequencing or data management. Sulston was there, together with LMB colleague Bart Barrell standing in for Sydney Brenner. ‘The mood swung from extreme scepticism to confidence it could be done but should it be done? There was a lot of suspicion of the ‘big science’ approach. But overall the conclusion was positive.’ ‘I felt amazed that we were all sitting discussing making an attack on the human genome.’ But Sulston had no idea any such plans would affect his work on the worm.Sinsheimer didn't get his institute because of internal politics at the University of California but the idea had been sown and advocates like Walter Gilbert of Harvard University were dubbing it the grail of human genetics. By June 1986 the ideas were being discussed at a Cold Spring Harbor meeting on human genetics, but Gilbert's estimate that the project could cost $3 billion caused uproar with many listeners assuming that funds for biological research would diverted to it.But the US Congress had now seized on the idea so the momentum for a structure-based approach to the genome was unstoppable.The Human Genome Project (HGP) officially began in 1990 with a target of a complete sequence by 2005. The new Office of Genome Research became the National Center for Human Genome Research, headed by Jim Watson, with an annual budget of almost $60 million. In the UK, Brenner persuaded the MRC to launch a UK Human Genome Mapping Project, and in 1989 the MRC won an £11 million grant over three years.Jim Watson was developing a list of model organisms to drive the technology and convince people about the value of the project. Sulston returned from a meeting with Watson who had given support to Sulston and his colleague Bob Waterston at the University of Washington at St Louis, for going ahead with the worm. In a state of great excitement, he went straight from his plane to the LMB and its director, Aaron Klug. ‘We're going to sequence the worm,’ he said. ‘Oh, no!’ Klug replied. But Klug quickly gave his support and Sulston believes his initial concerns were to make sure he knew what he was up against. For the first time in 20 years at the LMB, Sulston had to write a grant proposal for £1 million to sequence 1.5 megabases-just 3 per cent of the genome.The funding agencies gave Sulston and Waterston everything they asked for. ‘I still have the notification from the MRC, a classic missive. It was a really big grant for them over £1 million – and it came in the form of a hand-scrawled fax.’But Watson kept up his pressure on the MRC to fund more sequencing work. After one visit, Klug got the MRC's permission to talk to Bridget Ogilvie, the new director at the Wellcome Trust which in 1992 had more than doubled its budget through the sale of shares it owned in the pharmaceutical company, the Wellcome Foundation. She initially thought the Trust could provide £2 million to support him but very quickly realized it could do much more than support his work at the LMB.‘The year of 1992 was completely insane. It was one of those moments in one's life when one feels swept along like a leaf on the stream, he writes.’ The Wellcome TrustThe Wellcome Trust had decided to build a new sequencing centre at Hinxton, near Cambridge, of which Sulston would be director, to make an attack on the human genome.Fig. 2Genome legacy: the Sanger Centre at the Wellcome Trust genome campus in Hinxton, near Cambridge, that has made a major contribution to the human genome sequence.View Large Image | View Hi-Res Image | Download PowerPoint SlideA proposal was quickly developed for a grant of £40–50 million. The plan was to complete the worm within five years together with the yeast Saccharomyces cerevisiae, alongside the international consortium, and sequence the first 40 million bases of the human. The Wellcome Trust governors considered the proposal and agreed to fund it, ‘just like that,’ says Sulston. The MRC also came up with a grant of £10 million over five years to finish the worm sequence.But a much bigger change in his life than starting sequencing was the business of taking on new people. ‘I had never supervised more than one technician before, and hadn't made a very good job of that. It took me a while to realize that going into sequencing was going to lead to a big management structure,’ he says. But, in spite of early concerns by his friends and colleagues, he succeeded.By 1993 the collaboration on the worm was not only the most productive genome sequencing operation in the world, but the biggest. ‘But as we began to establish our reputation, the first signs had appeared of a belief that private enterprise could do as well or better than the public project, and could do it quicker and more cheaply’.Emboldened by their own success, Sulston sought to ramp-up funding to speed-up sequencing but found the agencies jittery. They had already committed substantial sums and cheaper and faster technologies might be developed. ‘It's their one failure of nerve,’ Sulston now believes – no new technologies were forthcoming, just incremental improvements – and new funds might have helped stall the private challenge to the HGP which came as a bombshell early in May 1998.Word had got out that Craig Venter, who had left the NIH in 1992 to found the Institute for Genome Research (TIGR), had got industrial backing to sequence the human genome which he aimed to complete in three years. Frantic phone calls and emails followed between the HGP players. Michael Morgan, programme director at the Wellcome Trust, was called by Jim Watson in a taxi crossing London. ‘What are we going to do?’ he asked. Sulston recounts the serious worries that the news brought, the US reaction of cautious welcome and his own deep concerns about the prospect of a privatized genome. A major eye-opener for Sulston was the power of public relations. Venter had given his story to the New York Times which ran it on May 10, the day before his press conference, where he announced that it might be better if the HGP left the human sequence to him and they turn their attention to the laboratory mouse.Many stories ran that Celera, the new company, could carry out the project more cheaply and more quickly than the HGP which met with great interest amongst politicians in the US scrutinizing federal spending and value for money. ‘The penetrative power of Celera's PR had so convinced the newspapers, and through them everyone, including many of my fellow scientists, that my own truths counted for nothing… The only recourse is to compete on the PR front in the first place. I found that a profoundly depressing thought.’But the Wellcome Trust came up with a feisty response and gave Sulston a big boost in funds. ‘We have to do this,’ the governors said, when they realised public access to the genome might be at stake. The news also bolstered the NIH which increased Waterston's funding. The HGP was fighting.The story describes the raw politics that saw simultaneous publication of two draft sequences in different journals last year. Sulston's uncompromising stand on a public genome certainly caused some difficulties for his colleagues but his book champions its virtues. Historians will find much of interest, as will anyone else with an interest in modern biology. It's a riveting read." @default.
- W2014666135 created "2016-06-24" @default.
- W2014666135 creator A5023790466 @default.
- W2014666135 date "2002-04-01" @default.
- W2014666135 modified "2023-10-14" @default.
- W2014666135 title "A human genome story" @default.
- W2014666135 doi "https://doi.org/10.1016/s0960-9822(02)00774-1" @default.
- W2014666135 hasPublicationYear "2002" @default.
- W2014666135 type Work @default.
- W2014666135 sameAs 2014666135 @default.
- W2014666135 citedByCount "1" @default.
- W2014666135 countsByYear W20146661352012 @default.
- W2014666135 crossrefType "journal-article" @default.
- W2014666135 hasAuthorship W2014666135A5023790466 @default.
- W2014666135 hasBestOaLocation W20146661351 @default.
- W2014666135 hasConcept C104317684 @default.
- W2014666135 hasConcept C141231307 @default.
- W2014666135 hasConcept C197077220 @default.
- W2014666135 hasConcept C54355233 @default.
- W2014666135 hasConcept C70721500 @default.
- W2014666135 hasConcept C78458016 @default.
- W2014666135 hasConcept C86803240 @default.
- W2014666135 hasConceptScore W2014666135C104317684 @default.
- W2014666135 hasConceptScore W2014666135C141231307 @default.
- W2014666135 hasConceptScore W2014666135C197077220 @default.
- W2014666135 hasConceptScore W2014666135C54355233 @default.
- W2014666135 hasConceptScore W2014666135C70721500 @default.
- W2014666135 hasConceptScore W2014666135C78458016 @default.
- W2014666135 hasConceptScore W2014666135C86803240 @default.
- W2014666135 hasLocation W20146661351 @default.
- W2014666135 hasOpenAccess W2014666135 @default.
- W2014666135 hasPrimaryLocation W20146661351 @default.
- W2014666135 hasRelatedWork W143076436 @default.
- W2014666135 hasRelatedWork W1489381018 @default.
- W2014666135 hasRelatedWork W1775134175 @default.
- W2014666135 hasRelatedWork W1967550999 @default.
- W2014666135 hasRelatedWork W1974425660 @default.
- W2014666135 hasRelatedWork W2012094124 @default.
- W2014666135 hasRelatedWork W2017432340 @default.
- W2014666135 hasRelatedWork W2017810680 @default.
- W2014666135 hasRelatedWork W2032032325 @default.
- W2014666135 hasRelatedWork W2038752831 @default.
- W2014666135 hasRelatedWork W2043041070 @default.
- W2014666135 hasRelatedWork W2049484519 @default.
- W2014666135 hasRelatedWork W2052735635 @default.
- W2014666135 hasRelatedWork W2054484012 @default.
- W2014666135 hasRelatedWork W2069610340 @default.
- W2014666135 hasRelatedWork W2142936477 @default.
- W2014666135 hasRelatedWork W2163977894 @default.
- W2014666135 hasRelatedWork W2177298319 @default.
- W2014666135 hasRelatedWork W2275824291 @default.
- W2014666135 hasRelatedWork W3033835506 @default.
- W2014666135 isParatext "false" @default.
- W2014666135 isRetracted "false" @default.
- W2014666135 magId "2014666135" @default.
- W2014666135 workType "article" @default.