In the week in which the first definitive translations of the human genome are published, Kevin Davies looks at the implications of understanding the language of the Lord.
One of the most humbling of scientific achievements was marked this week by the publication of two quite extraordinary issues of the journals Nature and Science . These volumes provide the first definitive translations of what former president Bill Clinton hailed (somewhat prematurely) last June as "the language in which God created life".
The public Human Genome Project, which featured a major contribution from Sir John Sulston's team at the Sanger Centre in Hinxton, near Cambridge, got off to a cautious beginning in 1990. It was sparked into life in May 1998, when J. Craig Venter, the controversial DNA sequencer, founded a private company called Celera Genomics to complete the sequence years ahead of schedule. The ensuing rivalry threatened to sully the sanctity of the research, before a modicum of decorum was belatedly restored to the proceedings, culminating in the joint White House celebration last summer. Debate as to the relative merits of the two sequences is likely to resonate for some time. In fact, the genome sequence is still not complete - it will take two or three more years. But why quibble over a few gaps and ambiguities amid a string of 3 billion letters of DNA code that could fill 1,000 telephone directories?
Fifty years after a cocky American named James Watson arrived in Cambridge with the naive notion of discovering the structure of DNA, the initial sequencing of the human genome is a fitting climax to a spectacular century of discovery. "This is just half-time for genetics," says Eric Lander, director of Massachusetts Institute of Technology's Genome Centre. "It started about 1900 (with the rediscovery of Gregor Mendel's fundamental laws of heredity) and the really interesting second half of the game is about to begin." Writing in this week's Nature , Lander and colleagues present a mesmerising 65-page tour of the human genome.
The final gene tally is surprisingly small - our proud species contains a paltry 30,000 genes, barely twice the number found in the fruit fly or nematode worm. With the genome sequence essentially complete, scientists are well on the way to compiling the genomic parts list of the human body.
Over the past 12 months, the public genome consortium has released the raw DNA sequence nightly over the internet, enabling researchers to track down dozens of disease-related genes in a matter of weeks, rather than years. With a steady stream of genes being discovered for common disorders such as Parkinson's disease, diabetes, obesity, heart disease and cancer, exciting clues have emerged to treat these devastating diseases. For example, genetic findings in Alzheimer's disease have dramatically enhanced our understanding of the brain's physiology and raised hopes that an effective vaccine can be developed.
From Aids to schizophrenia, the DNA sequence surveys of today are laying the groundwork for the drug discoveries of tomorrow. The genome project will usher in irrevocable changes in the practice of medicine. Twenty years from now, biotech companies will custom-sequence your DNA, which you will be able to view on a nicely packaged DVD: 999 letters out of every thousand will look identical to the genome sequences reported this week, but the 1,000th letter might be different - the genetic equivalent of a typographical error; perhaps a G instead of a T.
Although it sounds trivial, there are some 3 million of these single-letter differences between your genome and anybody else's - differences that hold the key to understanding why you might suffer from migraines and high blood pressure, while my family is prone to arthritis and short-sightedness. From Iceland to the south Atlantic, Finland to the Philippines, scientists are spanning the globe in search of remote, isolated populations in whom it is easier to associate specific DNA changes to common diseases such as asthma, diabetes and heart disease. In the process, they are cataloguing thousands of variations that determine our ability to respond to various classes of drugs. DNA screening will reveal which diseases we are most susceptible to and which drugs offer the best chance of success.
Our growing mastery of the genome also bodes well for gene therapy that, despite ten years of intense research on hundreds of patients, has resulted in only one successful trial. By 2020, scientists predict, we could see the first attempt at using gene therapy to permanently correct disease genes in the human germline, so that a patient no longer passes on that gene.
The most intriguing aspect of the sequence is what it might tell us about our own species. The human genome is like a 3-billion-year-old excavation site, replete with buried secrets of our evolutionary past. DNA studies are revising our ideas of when and where modern humans arose and migrated across the globe. But DNA can also tell us how our species came into existence. We are almost 99 per cent identical at the DNA level to chimpanzees, leading some scientists to ask whether a meticulous comparison of the human sequence with that of our closest primate cousins can reveal clues to our species' unique qualities - the ability to walk, talk and sequence our own genome.
The Human Genome Project also promises to unleash profound insights into the workings of the human brain by uncovering genes that contribute to human behaviour and personality. Although the sequence has not immediately divulged the identities of the putative "gay gene" or the "maths gene", we are on the brink of discovering genes for personality traits and mental illness. The Icelandic biotech company Decode Genetics announced last November that it had discovered a gene for schizophrenia. Identifying the factors responsible for such profound alterations in the human brain could yield greater insights into the human mind. As we learn more about the genes that shape various complex human traits and diseases, the notion of future generations selecting characteristics for their children edges uncomfortably closer. The era of designer babies arrived last year with the birth in the United States of Adam Nash, born to doting parents after pre-implantation genetic diagnosis with the express purpose of providing a life-saving bone marrow transplant for their fatally ill daughter.
Visions of would-be parents selecting traits for their children like dishes off a restaurant menu is anathema to many, although in time attitudes may soften. But there are downsides to divining our future from DNA. We all - without exception - carry dozens of misspellings in our genes that modify our risks to various diseases. Insurance companies will feel entitled to use DNA tests in much the same way as they consider age, sex, occupation and lifestyle. Will you be eligible for life insurance if you carry a genetic proclivity for Alzheimer's disease? Will you qualify for health insurance if you carry a susceptibility gene for colon cancer? Will you keep your job if you are genetically predisposed to depression? Francis Collins, head of the Human Genome Project, says: "We do not get to choose our genes, so our genes should not be used against us." The need for genetic privacy protection is a concern now that the genome is complete.
Since the launch of the project in 1990, commentators have likened the quest to the Apollo moon landings. "Putting a man on the moon is the easy part," says geneticist Sydney Brenner. "It is getting him back that is the problem." The Human Genome Project has set the foundation for a spectacular century of genetic discovery, but the most important challenge of all - to ensure that this information is used wisely and equitably for the benefit of humankind - begins now.
Kevin Davies is editor-in-chief of Cell Press and author of The Sequence: Inside the Race for the Human Genome , published this week by Weidenfeld & Nicolson, ?20.00.