The leaders of two competing teams of scientists stood shoulder to shoulder with President Clinton yesterday to announce they had simultaneously assembled the world's first working drafts of the entire human genetic code.
The dual achievements, presented at a gala White House ceremony, culminate a voyage of discovery that began 144 years ago when an Austrian monk named Gregor Mendel used pea plants to discover the basic laws of inheritance. More immediately it marks the end of an arduous, 10-year, $2 billion international effort to identify and place in order all 3.1 billion molecular "letters" of DNA residing inside virtually every human cell--the human genome.
Scientists and world leaders yesterday compared the feat to such paradigm-shifting human accomplishments as Isaac Newton's epochal discoveries in physics, Lewis and Clark's first mapping of the continental United States and the 1969 landing of men on the moon.
"Without a doubt, this is the most important, most wondrous map ever produced by humankind," Clinton told a packed East Room audience of scientists, members of Congress, health care advocates and ambassadors from several of the countries that helped with the massive effort.
The project's completion, Clinton said, "is a stunning, humbling achievement."
The human genome is a twisted strand of biological text that carries all the instructions for making and growing a human being. Errors in that text cause or contribute to the vast majority of human diseases, and the genome has an enormous influence on the quality of each person's life and the timing and circumstances of each person's death.
Experts predict that a full explication of the code will usher in a new era of molecular medicine, in which scientists will develop novel treatments and vaccines that target the most basic underpinnings of disease. Moreover, by comparing the human code to those of other organisms, including bacteria, plants, fish and mice, scientists will be able to tell with unprecedented accuracy the story of how human beings arose and evolved on Earth.
British Prime Minister Tony Blair, who participated in yesterday's ceremony via videoconference from No. 10 Downing Street, called the unveiling of the human genome "a revolution in medical science whose implications far surpass even the discovery of antibiotics." About one-third of the genome effort was completed by scientists in Britain, with funding largely provided by the nonprofit Wellcome Trust.
Yesterday's joint announcement also marked the apparent resolution of what had become an increasingly embarrassing conflict between publicly funded scientists around the world who had been working on the genome project since 1990 and an upstart biotechnology firm in Rockville that threatened to steal much of the project's glory by overtaking the effort in its final months.
Basking in the glow of accolades from Clinton, Blair and scientific luminaries from around the world, the leaders of those two competing efforts repeatedly shook hands and exchanged lavish compliments yesterday. The two projects, which took substantially different approaches to achieve the same scientific goal, promise to offer complementary benefits for the public and a quicker path to understanding and curing diseases, both said.
"I'm happy that the only race we're talking about today is the human race," said Francis S. Collins, chief of the National Human Genome Research Institute at the National Institutes of Health and the leader of the international Human Genome Project.
J. Craig Venter, the maverick president of Celera Genomics Corp., which hopes to profit by selling genome information to pharmaceutical developers and research scientists, thanked Collins for his statesmanship and described the overwhelming sense of unity he felt upon viewing the complete human blueprint at last.
"For the first time," Venter said, "our species can read the letters of our own genetic code."
Venter said his project used DNA taken from five people, including Hispanic, African American, Caucasian and Asian individuals, "out of respect for the diversity that is America, and to help illustrate that the concept of race has no genetic or scientific basis."
The publicly funded genome represents a "consensus" sequence that is a composite of a dozen anonymous people selected from about 100 volunteers who donated blood in response to advertisements years ago.
As further evidence that a significant detente had been reached between the two teams, Collins and Venter confirmed for the first time that they were coordinating efforts to publish the technical details of their work in simultaneous journal articles before the end of the year. They also said they were planning a conference, to be convened by early next year, at which the two teams would compare their results and weigh the pros and cons of their respective methods.
"Both of us have felt disheartened" by the recent emphasis on their disagreements, Collins said, which have largely centered on the extent to which data compiled by Venter's company would be made freely available to the public. "Now we can put behind us this chapter that I hope history will not be very interested in."
Venter said he would make Celera's raw data available to the public by the end of the year. The company does not plan to profit from those findings, he said, but from the sale of "value-added" genetic information created by running the genome data through the company's huge bank of supercomputers.
Even as scientists and officials celebrated the passing of what the White House dubbed "a milestone for humanity," a few sober commentators reminded the public that the mere elaboration of the human genetic code was but the beginning of a new era of biology and would not lead to instant benefits.
For one thing, the sequencing job is not really done. The publicly funded "working draft" includes about 97 percent of the genome's 3.1 billion units, of which about 85 percent have been placed in order. About half of that sequence is considered highly accurate, and the rest still needs to be "spell-checked" a few more times.
It is more difficult to say how comprehensive the Celera sequence is since the company has not released its raw data yet and has relied in part on the imperfect public database. Venter has described it as "99 percent done."
Even after the sequence is complete, many hurdles remain before it can be translated into medical benefits. Only about 3 to 4 percent of the human genome is believed to constitute actual genes, the units of biological information that are passed down from parent to child and that influence everything from eye color to temperament. Scientists still face a major task in finding those genes among the body's millions of lines of apparently meaningless code, commonly known as "junk DNA."
No one even knows yet how many human genes there are, with estimates ranging from about 38,000 to more than 120,000.
After those genes come to light, scientists will be challenged to understand how they influence health and disease, how they interact with other genes, how their activity is modulated by various regulatory elements in the genome, and how to design drugs or other strategies to correct deficiencies or prevent the expression of harmful traits.
"People say we can read it. We can't read it. We have the book, and now we've got to learn how to read it," said James Watson, whose co-discovery of the structure of DNA in 1953 heralded the beginning of modern genomics and who served as the first director of the Human Genome Project.
"It's like inventing the printing press," Watson said. "That's great, but let's print a book now. We'll shout 'hurrah' when we save lives."
Earlier, Clinton paid special tribute to Watson by reading a sentence from Watson's seminal paper with Francis Crick that described for the first time how DNA was built, calling the passage one of the great understatements in the history of science.
" 'This structure has novel features which are of considerable biological interest,' " Clinton read, to laughter. Then he turned to Watson: "Thank you, sir. How far we have come since that day."
Also largely unresolved are many of the ethical, legal and social issues that are sure to arise as the human genetic code becomes better understood and more malleable in researchers' hands.
Surveys indicate that many people consider genetic information to be exceedingly private and deserving of special protections from the eyes of government agencies, employers or health insurers. Some of the public is also concerned that knowledge gained from the genome project will allow scientists to create "designer babies" and perhaps inaugurate a new high-tech era of eugenics.
A CNN/Time poll released yesterday morning found that almost half of Americans believe there will be negative consequences from the Human Genome Project.
Congress has already passed one law that provides some protections against genetic discrimination in group health insurance plans, and Clinton last year signed an executive order outlawing genetic discrimination in the workplace for federal employees. Several bills are now awaiting congressional action that would strengthen those kinds of protections for a broader swath of the American public.
As originally conceived, the genome was not supposed to have been mapped completely until 2005. But competition from Celera spooked the publicly funded scientists and led everyone involved to speed up their work. Although the genome remains incomplete, both teams decided their drafts were in good enough shape to justify a public celebration. A complete product, accurate to 99.99 percent, is expected from the public project within two years and perhaps sooner from Celera.
Though barely civil for much of the last two years, the two groups cooperated yesterday in making the announcement so as not to mar a triumphal moment in science. Venter and Collins both credited Ari Patrinos for mediating an amicable resolution to their long-simmering conflict. Patrinos is head of the genome project at the Department of Energy, a significant but relatively unsung participant in the project.
Patrinos said he invited the two to his home for pizza and beer on May 7. That meeting was followed by three others, also in his home.
As it became clear that a joint announcement would be possible last week, government staffers started the difficult process of coordinating details with the White House and with the Securities and Exchange Commission, which didn't want advance word of the announcement to get out until after the close of the stock markets on Friday. Despite all the attention, Celera's stock dropped 11 percent yesterday.
Clinton acknowledged that it will take time for the genome project to generate substantial benefits. He looked sad as Collins described attending the funeral, over the weekend, of his young sister-in-law, who died of breast cancer.
But the president said he believes mankind is on the threshold of change. "It is now conceivable," he said, "that our children's children will know the term 'cancer' only as a constellation of stars."
Contents of the Code
The human genome is wound into two sets of chromosomes, one inherited from the mother and one from the father. Unraveled, the DNA would stretch for six feet.
About 38,000 to 120,000 genes carry the codes for making proteins that perform all life functions.
3.1 billion DNA subunits called bases come in four varieties, abbreviated A, T, C, G. These letters write the blueprint of human life.
Using the Code
Some potential applications for the decoded human genome:
Predict whether a person is likely to suffer from a specific disease.
Tailor drug prescriptions by determining how individuals will respond to medicines.
Alter patients' genetic material to fight or prevent disease.
Prevent genetic defects from being transferred to future generations.
Broaden the understanding of human evolution.
Human Genome by the Numbers
Number of "letters" of genetic code.
97% to 99%
Percentage of genome letters identified so far.
Percentage of those that have been assembled in order.
Approximate accuracy of public version.
Accuracy goal at completion in two years.
Percentage whose function remains unknown.
Number of genome letters being added to public database every second.
Approximate amount spent in 10 years on public and private genome projects.
Number of people whose genes are being sequenced by the public and private efforts.