Two competing teams of scientists proclaimed Monday they have completed rough drafts of the human genome–nature’s blueprint for creating and sustaining life–after a 10-year, multibillion-dollar effort that has been called biology’s version of the splitting of the atom. But cracking the human genetic code promises to change the future even more profoundly.
Assembling the catalog of the book of life is a staggering technical achievement that seems sure to change forever how we humans look at ourselves. But the word “future” should not be lost in all the hyperbole and excitement over the announcement.
Despite Monday’s White House news conference, with President Clinton announcing “A day for the ages,” what researchers now have is a string of 3 billion letters that must be read to learn where their patterns spell out genes. Scientists don’t even know how many genes are among them. In a betting pool set up by one scientist recently, estimates ranged from 34,000 to 140,000.
According to the archive of genetics, the Online Mendelian Inheritance in Man, a total of 11,722 genes have been discovered and characterized thus far. That’s an impressive number, but only a third of the minimum estimate. There’s a long way to go.
Genes and the environment work together to shape who we are, and in the years ahead studying that interaction will be possible. A gene is a sequence of DNA that is a recipe for a single protein. These proteins join together by the thousands to build tissues, organs and finally whole organisms.
But the purpose of most of the genes in the human genome seems to be regulating the workings of the other genes.
The story gets complicated further because 97 percent of our genome does not consist of protein-coding genes at all. The genome is actually an archive of human evolution and consists of the preserved genes we share with other animal species–chimps, fruit flies, even common brewer’s yeast. But also preserved is the detritus from millions of years–failed genes, dead genes, viral genes–all the strange entities called pseudogenes, retropseudogenes, satellites, minisatellites, microsatellites, transposons and retrotransposons–collectively referred to as “junk DNA.”
All of it had to be sequenced, though, and the sequence is eventually expected to revolutionize knowledge of the human body (just one small aspect, DNA fingerprinting, comes out of junk DNA and already has revolutionized forensics) and to raise biotechnology to one of the century’s major industries.
Finding the total sequence of all the DNA subunits in our cells means science can get to the next stage: Trying to find what it all means.
It is suspected that humans share 99.9 percent of their DNA, meaning that of the 3 billion letters in the genetic code, each of us differs by about 300,000. Those determine our individuality, our talents, and our susceptibility to diseases, among other things. Having the entire sequence and its relatively few variations will enable medical science to truly treat us as individuals.
Dr. Francis Collins, head of the Human Genome Project of the National Institutes of Health, said that having the sequence allows humans for the first time to read “our own instruction book. Today, we celebrate the revelation of the first draft of the human book of life.”
Standing with the president and Collins was scientist-entrepreneur J. Craig Venter, whose upstart biotech company, Celera Genomics, of Rockville, Md., was widely viewed as having forced a last-minute truce with the government by having earlier announced it had completed the sequence and would be providing it to subscribers.
The truce includes the publication of both groups’ versions of the genome at the same time in the same journal. But there is no reason to believe that a breakthrough has been achieved over the issue that wrecked previous conciliation efforts: access to the data.
President Clinton made the White House announcement, for which he was joined by British Prime Minister Tony Blair via satellite transmission.
Said Blair: “Let us be in no doubt about what we are witnessing today: A revolution in medical science whose implications far surpass even the discovery of antibiotics. [This is] the first great technological triumph of the 21st Century.”
As it has from the beginning, a group of hundreds of government scientists from the U.S., Britain, France, Germany, Japan and China who have been working in 16 centers around the globe will keep downloading sequence data every 24 hours on the Internet site GenBank, where it is freely available to researchers. Celera has sought restrictions on access to preserve its interest in profiting from the data by interpreting it.
Computer technology has speeded up sequencing exponentially. For example, a major sequencing center produced 600 million letters last year. In comparison, Venter expects to produce more than a hundred million letters of the genetic code every 24 hours–he will be able to do in a week what recently took a year.
Venter said his company has mapped the genetic codes of five people–three women and two men–of different races. Scientists who have studied the maps were unable to tell one ethnicity from another.
“We’ve shown the concept of race has no scientific basis,” Venter said.
In London, Dr. Michael Dexter of Britain’s Wellcome Trust, part of the public project, said: “Mapping the human genome has been compared to putting a man on the moon. But I believe that in terms of the future impact on society, the human genome project will be seen as the outstanding achievement, not only of our lifetime, but perhaps in the history of mankind.”
Longtime observers on Monday struggled for perspective about what should be considered a great human accomplishment.
“What’s being presented today is very raw,” said Sheldon Krimsky, professor of urban environmental policy at Tufts University, Medford, Mass. “The federal program won’t be completed for a couple years, so they have only a partial sequence. Celera has what they claim is a complete sequence, but with gaps in it. In the rush to be first, both sides are claiming victory, but it’s really not so much a scientific breakthrough as a symbolic milestone–the end of the beginning.
“Any great discovery will come not only from the genetic sequence, but from the ability to use that in some way to really improve human health. That will be the real test of the information.”
Unlike other scientific projects, the Genome Project allocated 5 percent of its budget for lawyers, ethicists and other nonscientists to discuss what it was doing and avoid misuses of the work.
Chicago attorney Lori Andrews, professor and director of the Institute of Science, Law and Technology at the Chicago-Kent College of Law, was chosen to chair the federal advisory panel, The Working Group on Ethical, Legal and Social Implications of the Human Genome Project.
That panel was regarded as a jewel in the project’s crown, but Andrews resigned when she decided that her group was little more than window dressing, created to deflect criticism from the scientists.
“We are close to having the entire sequence of a human, but what do we really know?” she observed in reaction to Monday’s announcements.
“We basically know the genetic alphabet, the string of 3 billion of the letters A, C, G and T, representing the chemical bases adenine, cytosine, guanine and thymine. It’s a four-letter alphabet instead of 26. But we are nowhere near being able to readily write poetry with that alphabet.
“The Human Genome Project is an important scientific achievement which could lead to measures to treat the more than 5,000 diseases that have a genetic basis. But in the meantime, the project has enhanced our ability to diagnose hundreds of genetic diseases while we still can’t treat them.
“Genetic testing has created a group of people dubbed the `asymptomatic ill’ who currently are healthy but feel they have a sword of Damocles hanging over them because they have learned they have an increased chance of cancer, say, later in life.”
In Sheldon Krimsky’s view, the idealistic aims of the Human Genome Project–and the $3 billion in public funds allotted to it–seem somewhat strained. As he sees the near-future: “For molecular biology, it means infusions of federal and private dollars because the sequenced human genome defines a locus of action and creates a mythology that something new and dramatic has happened.
“For the private sector, it symbolizes untapped wealth, namely the cornucopia of drugs and assays that the code is supposed to reveal.
“For new biotech startups, it means venture capital will pour in. For day traders, it means watching stock prices rise and then fall precipitously, trying to buy and sell during this period of intense media attention to what essentially is the final stage of a routinized and highly mechanical process.
“For Third World nations, it means the U.S. will hold the intellectual property rights over any commercial applications of this information–which, after all, is part of the common human heritage.”
As for the improving of the human condition, attorney Andrews is keeping her eyes open for trouble.
“Increasingly, insurers and employers want to roam around in people’s genes,” she cautioned . “A recent legal case alleged that the Lawrence Berkeley Lab tested African-American employees for the sickle-cell anemia gene without the workers’ knowledge or consent.
“And a survey of mid- and large-size companies by the American Management Association last month found that 30 percent of employers collected genetic information on employees.
“`Gattaca,’ here we come,” she said, referring to the anti-utopia science-fiction movie in which DNA matching becomes the tool the Big Brother uses to control the population.The HGP-Celera feud will probably be forgotten in a few years, but it represents the increasing privatization of science. Accordingly, the number of intellectual property lawyers in the U. S. is growing faster than the amount of research, the journal Science reported recently.
The bizarre race in which one contestant posts nightly results and the other keeps its progress secret has demonstrated the galvanizing power of competition in achieving a complex goal. But it has threatened to sabotage what had been considered one of the most altruistic international efforts of all time.
In biology, a science not normally known for cooperation, the federally funded, multinational genome collaboration was highly unusual. It formally began in 1990 with a lofty goal: not only to map the human genome by 2003, but to make the map available to the public.
As such, the genome consortium of academic centers supported largely by the National Institutes of Health, the Department of Energy and the Wellcome Trust, has immediately posted the information, thus immunizing it from patent hounds.
It was crucial to the project’s planners in the 1980s that success would rely on cooperation and on technologies that hadn’t been invented yet, if there was any hope of sequencing all the human DNA in 15 years.
But the pioneers never counted on being pressured by a brilliant former NIH genome scientist, Venter, who left the government and two years ago founded Celera, which claimed to have a speedy way of sequencing the genome at a fraction of the cost, and planned to market the information on its database to subscribers.
Negotiations between the two sides broke down in February amid acrimony over public access to the data versus Celera’s determination to protect itself from competitors.
There’s no denying that although Celera entered the race a full eight years behind the government, it seems to have crossed the finish line three years ahead of the schedule set by the HGP.
The consortium could have attacked Celera’s genome as being quick and dirty– it still has many small gaps and makes use of the consortium’s data–while declaring its own victory in providing the beginning-to-end “gold standard,” though it wouldn’t be completed until 2003.
The alternative, which it seems to have accepted, was to adopt Celera’s timetable. The government is, in effect, declaring victory and moving on.
As Clinton predicted at the end of Monday’s news conference:
“When we get this all worked out and we’re all living to be 150, young people will still fall in love, old people will still fight about things that should have been resolved 50 years ago, we will all on occasion do stupid things and we will see the unbelievable capacity of humanity to be noble.”
MILESTONES IN GENETIC RESEARCH
1866: Gregor Mendel, left, an Austrian monk, discovers the basics of heredity by breeding pea plants.
1910: Working with fruit flies, Thomas Hunt Morgan, left, discovers genes are organized along chromosomes.
1942: Researchers studying bacteria propose that genes are made of DNA, an acid found in the cell nucleus.
1953: James Watson, left, and Francis Crick find DNA’s double-helix shape.
1973: Stanley Cohen and Herbert Brown invent genetic engineering by transplanting a gene between bacterium.
1987: Scientists isolate genes that cause muscular dystrophy, cystic fibrosis, Huntington’s disease and breast cancer.
1990: Government-funded Human Genome Project begins, aimed at decoding the entire human genome by 2003.
1998: Privately funded Celera announces they will do a high-speed analysis of the human genome, completing it in 2001.
1999: Researchers in the Human Genome Project announce the complete sequencing of the first human chromosome (22).
2000: The Human Genome Project and Celera announce the human genome has been sequenced.
Source: Nature Magazine, Human Genome Project, KRT, American Medical Association
Chicago Tribune/David Constantine,Rick Tuma, Robert Dorrell
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