Scientists Reach Milestone in Mapping of Human Genome
WASHINGTON — In an achievement compared to Lewis and Clark’s mapping of the continent, two teams of scientists announced Monday that each has produced a draft version of the human genetic code.
The code, also known as the human genome, is the detailed instruction manual for the inner machinery of every member of our species. Scientists believe that having the complete genetic manual will give them a vital tool for fighting disease, maintaining health and perhaps extending human life.
The announcement means that the race between a private biotechnology company, Celera Genomics, and the publicly funded Human Genome Project has ended in a dead heat after two years of fierce and often bitter competition.
The joint announcement, which came in a transatlantic news conference held by President Clinton and British Prime Minister Tony Blair, followed weeks of secret negotiations between leaders of the rival factions: J. Craig Venter, Celera’s president and chief scientific officer, and Francis Collins, leader of the public project.
The ceremony was a moment of shared triumph and an official recognition that a new era in medical science has begun.
Clinton, speaking from the East Room of the White House, compared the achievement to the day two centuries ago that Thomas Jefferson met with explorer Meriwether Lewis in the same room to look at the first crude map of the North American continent.
The new genetic maps are of “even greater significance,” the president said. “Without a doubt, this is the most important, most wondrous map ever produced by humankind.”
Clinton and Blair spoke glowingly of medical advances--of new ways to prevent, diagnose, treat and even cure disease--based on knowledge contained in the 3 billion chemical building blocks or letters in the genome.
Blair, speaking from 10 Downing Street in London, was similarly awe-struck, predicting that the genetic map would bring changes in the first half of the new century as radical as those brought by computer technology in the last half of the century past.
Both leaders, however, expressed concern about the potential for abuse of the new knowledge through genetic discrimination as well as manipulation of human genetics without a clear understanding of the consequences.
“There is no point in arguing whether we’re comfortable with it,” Blair said. “It’s there. It’s something we now know. It has the potential to do good.”
Monday’s carefully orchestrated announcement followed delicate diplomacy between Celera and the public project conducted over beer and pizza in the private home of Ari Patrinos, the top scientist at the Department of Energy, which resulted in a truce in which both sides agreed to cooperate with one another.
White House aides were issued language alerts advising them that they could speak of “cooperation” and “coordination” between the once-warring camps, but not “collaboration.”
Still, it was clear on Monday that the two sides had broken from a history of animosity to praise one another--like athletes rising above the bruises and trash talk of a close playoff game to honor the skills of their opponents.
Celera’s Venter and the public project’s Collins shared the stage with Clinton at Monday’s White House ceremony. As part of their agreement, the two camps will publish their detailed scientific findings simultaneously sometime later this year.
Both versions of the genome contain numerous gaps and misalignments that could take years to fill and correct; and both competing camps defined--and then redefined--their own finish line for their first, incomplete decoding effort.
Celera used the public data in assembling its draft of the genome, which makes its version the more complete of the two. Initially, the company’s genome will be provided only to paying subscribers, but Venter promised to make it available to academic researchers on the company’s Web site later this year.
Collins, who is director of the National Human Genome Research Institute, pledged that the public effort--carried out at 16 centers in six countries--would continue its work until the job is complete and error-free. That should happen, he said, by 2003, before the 50th anniversary of the discovery of the structure of DNA, the staircase-like double helix--the molecule of heredity in all living things.
“It is humbling for me and awe-inspiring to realize that we have caught the first glimpse of our own instruction book, previously known only to God,” Collins said. “Historians will consider this a turning point. Researchers in a few years will have trouble imagining how we studied human biology without the genome sequence in front of us.”
Venter said that Celera made a point of using samples of DNA from five individuals--three females and two males; Hispanic, Asian, Caucasian, and African American--”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 public project used pieces of genetic code from a dozen individuals.
Venter later explained to reporters why his company, part of PE Corp., and the public project had agreed to end their feud.
Basis for Truce
“If we’re going to be custodians of the genetic information and be trusted to analyze and interpret it,” he said, “we felt it was important for us to rise above the squabbles that you’ve read about and to act more at the level appropriate with this situation.”
The achievement is a vindication both for the public project, which began in 1990 amid much criticism and doubt, and for the upstart biotech company that was launched with the express purpose of finishing the genome first.
There remains considerable work left in completing the genome--in deciphering and listing all those chemical letters in order from samples of DNA contained in all 24 human chromosomes. Large chunks of genetic code, as much as 10% of it--cannot be deciphered with current technology. And other, smaller pieces will be decoded only over time and with much effort. Like a book with phrases, sentences and even whole pages missing, there are many gaps that need to be filled.
Still, the draft genomes will give users an enormous amount of usable information. Continuing the book analogy, it is better to have an instruction manual with occasional missing pages than to have no manual at all.
Indeed, there is wide agreement that even an incomplete text of the human genome is extremely valuable.
Yet, having the genome is just the beginning of decades of new discovery. It could be years before anyone can answer even such a basic question as how many human genes there are. Genes are small stretches of DNA that direct production of proteins. Current estimates range widely, from 30,000 to 140,000. And it will be decades before scientists understand how all those genes work over the lifetime of an individual, in illness and health and from conception to death.
With about 85% or more of the genetic code spelled out in either version, the result is a tool of immense power for both corporate and academic laboratories.
“We can see a majority of [the genes] now, and that’s pretty good,” said James D. Watson, who won the Nobel Prize as co-discoverer of the structure of DNA.
Scientists in pursuit of the mysteries of the human organism are eager to have the new information contained in the human genetic code. Many speak of the human genome with a reverence usually reserved for the spiritual. It is the code of codes, the Holy Grail of biology, the blueprint for humankind, the book of life.
It determines whether we are men or women, tall or short, brown-eyed or blue. It sets the shape of our kidneys, the form of our lungs, the architecture of our hearts.
Already genetic scientists can read a woman’s DNA to determine whether she is likely to develop an inherited type of breast cancer. Already they are attempting to override bad genes with good, in diseases like cystic fibrosis and hemophilia. Already they can capture human genes to produce natural hormones: insulin for the diabetic, growth hormone for the short of stature, red-cell-boosting erythropoietin for the anemic.
Coils of Complexity
The genome is written in a wonderfully compact four-letter code. Each letter--A, T, C and G--stands for a different chemical building block within the DNA helix, the common molecule of heredity in all species.
In human cells there are so many of these letters that it would take 100,000 pages of this newspaper to write them all out, even in the smallest type. They are strung out along tightly coiled chains of DNA within the chromosomes within the inner chamber or nucleus of most cells.
A small fraction of those letters, less than 5%, spell out the genes--the exact number of which won’t be known until the genome is completely deciphered and all the genes identified. The genes carry the instructions for the proteins that combine to construct the individual human being.
Celera and the Human Genome Project used two distinct methods for deciphering the human code.
To sequence an entire genome, it must be broken up into millions of tiny pieces. That’s because the current machines can only decode fragments that are 500 to 1,000 chemical letters long.
The public project, financed largely by the National Institutes of Health and the Wellcome Trust, a British charity, divided the task--divvying up pieces of the chromosomes among the 16 centers in six countries that make up the international Human Genome Project.
Celera has taken a different approach. Instead of dividing the work up into chunks of chromosomes, the company’s scientists broke up copies of whole genomes randomly into 26 million fairly small, overlapping pieces--a scattershot approach that is called the whole genome shotgun method. They then deployed a phalanx of supercomputers to assemble all those pieces together.
In April, Venter announced that the company had completed the decoding phase of the work of the first individual. But that still left the formidable, uncertain task of putting all those pieces together.
No genome center--public or corporate--had ever attempted a computerized assembly of so many DNA fragments on such a huge scale.
Celera made use of the public project data to help in its assembly, according to a company news release.
Cracking the code of the genome--listing all 3 billion in order--won’t fully explain how the human organism works nor how the genes interact with one another. That will be work enough to keep scientists busy for another century.
But as Stanford genetics professor David Botstein said: “Sequencing is essential, like the alphabet, like grammar. It is the beginning from which everything flows.”
Jacobs reported from Sacramento and Zitner from Washington. Times staff writers Peter G. Gosselin in Washington and Marjorie Miller in London contributed to this report.
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A Human Treasure Map
The genome is a map of the cell’s inner workings, of the chemicals that tell it how to behave. This map may one day allow researchers to figure out how cells work and how they can be altered to prevent and treat illness.
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THE GENOME:
The code is a long string of chemical building blocks represented by the letters A,T, C and G for adenine, thymine, cytosine and guanine.
A gene is a sequence of DNA that controls a cell’s function
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Sources: National Center for Biotechnology Information; Department of Energy
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At the Heart of a Revolution: the DNA Sequence
The working draft of the human genetic code would not have been possible without the development of highly automated technology, pioneered by scientists at Caltech in the 1980s.
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A stretch of DNA is copied, and fragments of all different lengths are generated. Each is labeled with one of four fluorescent dyes, one for each of the four chemical building blocks that make up DNA--represented by the letters A, T, C and G. The color is determined by the final building block in each fragment.
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The DNA of the first virus sequenced is slightly more than 5,000 bases long. The letters of the human genetic code would take up more than 500,000 times this space.
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A computer translates the dye colors into the A’s, Ts, Gs and Cs of the genetic code.
The soup of dye-labeled fragments is fed into a capillary, a hollow, gel-filled tube not much thicker than a hair. An electrical current pulls the pieces through the tube in order of length, the shortest first. A laser beam hits the dyes attached to the DNA fragments as they pass through the capillary, causing them to glow with a distinctive color. The order of the colors corresponds to the order of the chemical building blocks or letters in the original piece of DNA.
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* GENOME STOCKS
A look at some of the companies leading the genome-research efforts, and how their stocks have fared. C6
