The first draft of the Book of Humankind has been read
The Human Genome Project – the international project to identify all the genes of the human body – has completed the initial stage of the work. The information has been given away freely to the world – a vast and unique gift to celebrate the commonality of humankind.
The work, carried out in 16 centres across the world, means that 85% of the human genome has been accurately deciphered. Further work, still to be finally checked, means in total 97% of the human genome has been read.
The existence of this genetic map will lay the foundation for a revolution in medical diagnosis and treatment.
The project has been described as the biomedical equivalent of putting a man on the moon, but it is only now the real genetic exploration can begin, using the map provided by the Human Genome Project (HGP).
Dr Michael Dexter, Director of the Wellcome Trust, which committed £210 million to the Sanger Center, said the completion of the first phase of the work marked a medical landmark that would stand alongside or even eclipse other great scientific discoveries of the past.
“Mapping the human genome has been compared with putting a man on the moon, but I believe it is more than that. This is the outstanding achievement not only of our lifetime, but in terms of human history.
“A few months ago I compared the project to the invention of the wheel. On reflection, it is more than that. I can well imagine technology making the wheel obsolete. But this code is the essence of mankind, and as long as humans exists, this code is going to be important and will be used.”
Dr Michael Dexter Director of the Wellcome Trust
Dr Dexter cautioned that cures would not spring up overnight as a result of the work, but the blueprint of humankind would allow a vast range of new treatment approaches to be investigated.
“Our genes make us what we are as human beings. It’s these genes working together that maintain a healthy functioning body. Our genes make us susceptible or resistant to disease; tolerant or intolerant of medicines.
“What the sequence information will allow us to do is to identify precisely what genes go wrong when we develop disease. Once we know this We open up a tremendous number of potential therapies.”
Dr Michael Dexter
Information from the HGP is already being applied in the fight against specific genetic diseases such as muscular dystrophy, but knowledge about the whole genome will eventually lead to better diagnosis and treatment for a range of conditions from cancer to heart disease. The first fruits are likely to be in the field of new, more accurate, diagnostic tests, and later the development of personalised medicine, where treatments and drugs are based on a person’s individual genetic make up.
Dr John Sulston, Director of the Sanger Centre, said the British team was responsible for sequencing a third of the genome, but the project was a remarkable witness to a truly international collaboration.
It is fitting that almost 50 years after James Watson and Francis Crick first described the double helix of DNA in 1953, in Cambridge, their legacy is being laid before the world by Cambridge scientists.
Dr Sulston said knowledge of the human genome would have a far reaching cultural effect on mankind, beyond its many practical uses.
“One should not underestimate how important this event is in human history. Over the decades and centuries to come this sequence will inform all of medicine, all of biology, and will lead us to a total understanding of not only human beings but all of life. Life is a unity, and by understanding one part you understand another.
“When you look at all the possible combinations of all the variations in the human genome, of which there are possibly ten million, then the number of combinations vastly exceeds the number of particles in the known universe. We can be pretty sure, very sure, that we will never get two identical human beings unless they come from the same split egg, that is identical twins.”
Dr John Sulston, Director of the Sanger Centre
Dr Sulston said the wider message of the human genome pointed to two profound truths about humankind – the remarkable similarities between people, and with other life forms, and the wonderful differences between individuals.
“In every 1,000 of the genetic letters, there are two differences between people. Most of the letters of the code are the same between us – but that still leaves an awful lot of differences. My way of looking at it is that we should take both morals from it. We should certainly regard ourselves as similar and take responsibility for one another in that way, but we also have to respect our differences.
The scientific proof that humans are 99.9% similar was highlighted by Dr Dexter as a far-reaching cultural icon of the work. “We have powerful new ways to see what it is that makes each individual unique – but perhaps more importantly we have new tools to see what it is that makes us all the same. Our common humanity is set out in the wonderful spiral staircase that is our DNA And at last we can read its letters.”
Dr John Sulston
Dr Michael Morgan, Chief Executive of the Wellcome Trust Genome Campus, said sequencing the human genome provided a legacy that would be producing new treatments for generations to come.
“I think when we reflect on the sequencing of the human genome we will see this was the beginning of biology and medicine based on a fundamental understanding of the underlying processes of life. It is going to provide, for the first time in biology, a fundamental foundation on which everything in the future will relate to and, to an extent, be dependent upon.”
Dr Michael Morgan, Chief Executive of the Wellcome Trust Genome Campus
Like other scientists in the project Dr Morgan firmly believes that the genome sequence enhances the wonder of life, rather than reducing human beings to a collection of chemicals.
“I think there is something magical in knowing that all life on the planet, be it plant, bacterial or animal, is related in some way.
“The length of DNA in each human being If we added it all together, stretches from here to the sun and back many times. It think this is quite extraordinary and awe inspiring.”
Dr Michael Morgan
The Wellcome Trust and Sanger Centre believe that fears that the work could lead to the creation of designer babies, or people being refused insurance because of their genetic make up, are probably unfounded, but could be addressed by legislation. However, the potential gains far outweigh the potential risks.
“The ability to predict, which undoubtedly genetics at this level is beginning to bring more and more accurately, has to carry with it social responsibility.
“It’s absolutely no different from our recognition that people should be treated equally no matter what their skin colour is, no matter what their sex is, no matter what physical disabilities they may have. One’s genetic inheritance has got to be treated in the same way.
“We do have to recognise this and take specific regulatory steps to ensure people are treated similarly. It’s just an extension of human rights. We have to reaffirm that all people are equal and have human rights – that is very important.
“Our genetic inheritance sets limits on our capabilities, but the truth is that each individual has enormous potential which is not being met. No one, or society, should ever regard one individual as less than another because of their genetic inheritance. One’s genetic inheritance is something to be built on, celebrated, and if necessary overcome, rather than being enslaved to.”
Dr John Sulston
The current human genome information marks just the “end of the beginning” not a completion of the task. Detailed work will continue for at least the next two years filling in the gaps in the knowledge, to produce a “Gold Standard” reference sequence. However, even after that it is expected that a small number of genes will continue to be found for many years to come, as people minutely explore the more difficult to sequence stretches of human DNA.
The Wellcome Trust and the Sanger Centre support the suggestion already made to UNESCO that the human genome should be declared a world monument to be held in trust, freely available, for all humankind.
The other countries taking part in the HGP are America, Japan, France, Germany and China.
In a related announcement, Celera Genomics announced today that it has completed its own first assembly of the human genome DNA sequence.
“The two approaches are quite complementary. The public project and Celera plan to discuss the relative scientific merits of the methods employed by the two projects. In the end, the best approach may well be to use a combination of the methods for sequencing future genomes.”
Francis Collins Director of the US National Human Genome Research Institute
The international Human Genome Sequencing consortium includes scientists at 16 institutions in France, Germany, Japan, China, Great Britain and the United States. The five largest centres are located at: Baylor College of Medicine, Houston, Texas; Joint Genome Institute in Walnut Creek, California; Sanger Centre near Cambridge, England; Washington University School of Medicine, St. Louis; and Whitehead Institute, Cambridge, Massachusetts. Together, these five centres have generated about 82% of the sequence.
More information
The HGP consortium’s goal for the Spring of 2000 was to produce a working draft version of the human sequence, an assembly containing overlapping fragments that cover 90 percent of the genome and that were sequenced in ‘working draft’ form, i.e. with some gaps and ambiguities.
The consortium’s ultimate goal is to produce a completely “finished” sequence, i.e. one with no gaps and 99.99 percent accuracy. The target date for this ultimate goal had been 2003, but today’s results mean that the final, “stand-the-test-of-time” sequence will likely be produced considerably ahead of that schedule.
The public and private projects use similar automation and sequencing technology, but different approaches to sequencing the human genome. The public project uses a ‘hierarchical shotgun’ approach in which individual large DNA fragments of known position are subjected to shotgun sequencing (i.e. shredded into small fragments that are sequenced, and then reassembled on the basis of sequence overlaps).
The Celera project uses a “whole genome shotgun” approach, in which the entire genome is shredded into small fragments that are sequenced and put back together on the basis of sequence overlaps.
The hierarchical shotgun method has the advantage that the global location of each individual sequence is known with certainty, but it requires constructing a map of large fragments covering the genome. The whole shotgun method does not require this step, but presents other challenges in the assembly phase.
The Human Genome Project will now focus on converting the draft and near-finished sequences to a finished form. This will be done by filling the gaps in the working draft sequence and by increasing the overall sequence accuracy to 99.99 percent.
Although the working draft version is useful for the most biomedical research, a highly accurate sequence that is as close to perfect as possible is critical for obtaining all the information there is to get from human sequence data. This has already been achieved for chromosomes 21 and 22.
The cost of sequencing the human genome is sometimes reported as $3 billion. However, this figure refers to the original estimate of total funding for the Human Genome Project over a 15-year period (1990-2005) for a wide range of scientific activities related to genomics.
These include studies of human diseases, experimental organisms (such as bacteria, yeast, worms, flies and mice), development of new technologies for biological and medical research, computational methods to analyse genomes, and ethical, legal and social issues related to genetics.
The sixteen institutions that form the Human Genome Sequencing Consortium include:
- Baylor College of Medicine, Houston, Texas, USA
- Beijing Human Genome Center, Institute of Genetics, Chinese Academy of Sciences, Beijing, China
- Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany
- Genoscope, Evry, France
- Genome Therapeutics Corporation, Waltham, MA, USA
- Institute for Molecular Biotechnology, Jena, Germany
- Joint Genome Institute, U.S. Department of Energy, Walnut Creek, CA, USA
- Keio University, Tokyo, Japan
- Max Planck Institute for Molecular Genetics, Berlin, Germany
- RIKEN Genomic Sciences Center, Saitama, Japan
- The Sanger Centre, Hinxton, U.K.
- Stanford DNA Sequencing and Technology Development Center, Palo Alto, CA, USA
- University of Washington Genome Center, Seattle, WA, USA
- University of Washington Multimegabase Sequencing Center, Seattle, WA,USA
- Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, USA
- Washington University Genome Sequencing Center, St. Louis, MO, USA
In addition, two institutions played a key role in providing computational support and analysis for the Human Genome Project over the course of the past eighteen months. These include:
- The National Center for Biotechnology Information at NIH
- The European Bioinformatics Institute in Cambridge, UK
The assembly of the genome sequence across chromosomes was also assisted by scientists at the University of California, Santa Cruz, and Neomorphic, Inc.
