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Science after the sequence
1.
NEWS FEATURE
NATURE|Vol 465|24 June 2010 Vol SCIENCE AFTER THE SEQUENCE The completion of the draft human genome sequence was announced ten years ago. Nature’s survey of life scientists reveals that biology will never be the same again. Declan Butler reports. “W ith this profound new managed without it,” wrote one scientist. they thought that basic biological science had IllustratIon by Jonathan burton knowledge, humankind The survey, which drew most participants benefited significantly from human genome is on the verge of gaining through Nature’s print edition and website and sequences, only about 20% felt the same was immense, new power to was intended as a rough measure of opinion, true for clinical medicine. And our respondents heal. It will revolutionize the diagnosis, preven- also revealed how researchers are confronting acknowledged that interpreting the sequence is tion and treatment of most, if not all, human the increasing availability of information about proving to be a far greater challenge than deci- diseases.” So declared then US President Bill their own genomes. Some 15% of respondents phering it. About one-third of respondents Clinton in the East Room of the White House say that they have taken a genetic test in a med- listed the field’s lack of basic understanding of on 26 June 2000, at an event held to hail the ical setting, and almost one in ten has used a genome biology as one of the main obstacles to completion of the first draft assemblies of the direct-to-consumer genetic testing service. making use of sequence data today. human genome sequence by two fierce rivals, the When asked what they would sequence if they publicly funded international could sequence anything, many Sequence is just the start 69% Human Genome Project and respondents listed their own Studies over the past decade have revealed its private-sector competitor genomes, their children’s or that the complexity of the genome, and indeed Celera Genomics of Rockville, those of other members of their almost every aspect of human biology, is far Maryland (see Nature 405, were inspired by family (the list also included a greater than was previously thought (see Nature 983–984; 2000). the genome to few pet dogs and cats). 464, 664–667; 2010). It has been relatively Ten years on, the hoped- become a scientist Some are clearly impatient straightforward, for example, to identify the for revolution against human or change their for this opportunity: about 20,000 or so protein-coding genes, which make disease has not arrived — and research direction. 13% say that they have already up around 1.5% of the genome. But knowing Nature’s poll of more than sequenced and analysed part this, researchers note, does not necessarily 1,000 life scientists shows that of their own DNA. One in five explain what those genes do, given that many most don’t anticipate that it will for decades said they would have their entire genome genes code for multiple forms of a protein, each to come (go.nature.com/3Ayuwn). What sequenced if it cost US$1,000, and about 60% of which could have a different role in a variety the sequence has brought about, however, is would do it for $100 or if the service were of biological processes. “The total sequence was a revolution in biology. It has transformed offered free. Others are far more circumspect needed, I think, to allow us to see that our one the professional lives of scientists, inspiring about sequencing their genome — about 17% gene–one protein model of genetics was much them to tackle new biological problems and ticked the box saying “I wouldn’t do it even if too simplistic,” wrote one respondent. throwing up some acute new challenges along someone paid me”. A decade of post-genomic biology has also the way. Nature’s poll also gauged where the sequence focused new attention on the regions outside Almost all biologists surveyed have been has had the greatest effect on the science itself. protein-coding genes, many of which are likely influenced in some way by the availability Although nearly 60% of those polled said to have key functions, through regulating the of the human genome sequence. expression of protein-coding genes A whopping 69% of those who Which areas have benefited significantly from the and by making a slew of non-coding responded to Nature’s poll say sequencing of human genomes? RNA molecules. “Now we under- that the human genome projects stand,” wrote another survey respond- inspired them either to become a Basic biological research ent, “that, without looking at the scientist or to change the direction Basic medical research dynamics of a genome, determining of their research. Some 90% say that its sequence is of limited use.” Some Clinical medicine their own research has benefited big projects are under way to fill in from the sequencing of human Biotech & pharma the gaps, including the Encyclopedia genomes — with 46% saying that Computational biology of DNA Elements (ENCODE) and it has done so “significantly”. And the Human Epigenome Project, an Sequencing technology almost one-third use the sequence effort to understand the chemical “almost daily” in their research. 0 20 40 60 80 100 modifications of the genome that are “For young researchers like me Percentage of respondents now thought to be a major means of it’s hard to imagine how biologists controlling gene expression. 1000 © 2010 Macmillan Publishers Limited. All rights reserved
2.
Vol 465|24 June
2010 NEWS FEATURE What are the main obstacles to making use of the flood of How much would you pay to have your genome sequenced? sequencing data? More than one answer can be selected. More than $10,000 $10,000 I do not use sequencing Other Basic understanding of $1,000 data in my research (7.4%) genome biology $100 (21.3%) (34.6%) I would do it if it were offered free Ethical or legal constraints I wouldn’t do it even if on data access someone paid me (15.2%) 0 5 10 15 20 25 30 35 904 Percentage of respondents respondents How soon do you expect personalized medicine, based on 1,779 human genetic information, to become commonplace? responses Computing power Software or algorithms to It's already here (26.5%) process sequencing data 5–10 years (48.8%) 10–20 years 20–30 years More than 30 years Lack of qualified bioinformaticians Not in my lifetime (42.9%) 0 5 10 15 20 25 30 35 Percentage of respondents The biggest effects of the genome sequence, Bethesda, says that the institute is well aware population,” read one typical response. More according to the poll, have been advances in of the need for more bioinformatics experts, than one-third of respondents now predict the tools of the trade: sequencing technolo- better software and a clearer understanding of that it will take 10–20 years for personalized gies and computational biology. Technologi- how the differences between genomes influ- medicine, based on genetic information, to cal innovation has sent the cost of sequencing ence human health. He says the institute is become commonplace, and more than 25% tumbling, and the daily output of sequence planning to publish in late 2010 its next stra- even longer than that. Some 5% don’t expect it has soared (see Nature 464, 670–671; 2010). tegic five-year plan for the genomics field. One will happen in their lifetime. “Our understand- “Deep sequencing technology is now becom- possible solution to the computing challenge, ing of the genome will not come in a single flash ing a staple of scientific research. Would this which was discussed at an NHGRI workshop of insight. It will be an organized hierarchy of have occurred if it wasn’t for the technological in late March, is cloud computing, in which billions of smaller insights,” says David Haus- push required to finish the human genome?” laboratories buy computing power and storage sler, head of the Genome Bioinformatics Group read one response. in remote computing farms from companies at the University of California, Santa Cruz. such as Google, Amazon and Microsoft. The Green says that when the Human Genome Data dreams, analysis nightmares European Nucleotide Archive, Project was envisioned, scientific 13% Cheaper and faster sequencing has brought launched on 10 May at the Euro- leaders of the day predicted that its own problems, however, and our survey pean Molecular Biology Labora- it would take 15 years to generate revealed how ill-equipped many researchers feel tory’s European Bioinformatics the first sequence, and a century to handle the exponentially increasing amounts Institute in Cambridge, UK, will have sequenced for biologists to understand it. “I of sequence data. The top concern — named also offer labs free remote stor- part of their think they got that about right,” by almost half of respondents — was the lack age of their genome data and use own DNA. he says. “While we still don’t have of adequate software or algorithms to analyse of bioinformatics tools. all the answers — being a mere genomic data, followed closely by a shortage Given ten years’ of hindsight 10% of the way into the century of qualified bioinformaticians and to a lesser and the current set of obstacles, it’s no surprise with a human genome sequence in hand — we extent raw computing power. Other concerns that researchers now state somewhat mod- have learned extraordinary things about how include data storage, the quality of sequencing est expectations for what human genomics the human genome works and how alterations data and the accuracy of genome assembly. can deliver and by when. The rationale for in it confer risk for disease.” Commenting on the survey results, David sequencing and exploring the human genome Haussler agrees. “All that happened in the Lipman, director of the US National Center for — to revolutionize the finding of new drugs, first ten years is still just early rumblings of Biotechnology Information in Bethesda, Mary- diagnostics and vaccines, and to tailor treat- much more dramatic changes to come when land, says that the worries about data handling ments to the genetic make-up of individu- we begin to truly understand the genome,” he and analysis were an issue even in the earliest als — is the same today. But almost half of says. ■ discussions of the genome project. Perhaps, he respondents now say that the benefits of the Declan Butler is a senior correspondent at suggests, “there’s a sort of disappointment that human genome were oversold in the lead up Nature based in France. despite having so much data, there is still so to 2000. “While I do feel that the gains made Survey work was aided by Sara Grimme. much we don’t understand”. by the human genome project are extraor- See full survey results at go.nature.com/3Ayuwn. Eric Green, director of the National Human dinary and affect my research significantly, See Nature’s human genome special at Genome Research Institute (NHGRI) in I still feel that it was overhyped to the general www.nature.com/humangenome 1001 © 2010 Macmillan Publishers Limited. All rights reserved
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