Two buildings trimmed in nautical blue stand in a copse of trees on a little rise just off Montgomery County's main commercial drag. Car salesmen ply their trade across the street. From the outside, this place looks like nothing more than a pair of office buildings.
Indeed, thousands drive by daily without a clue that one of the boldest experiments in American business is unfolding a few yards from Frederick Road, the highway known a bit farther south as Rockville Pike.
At a stage of life when others dream of slowing down, this is the task that John Craig Venter, 52, has set for himself: to unravel the "book of life," the entire set of genetic instructions that make up a human being, and to do it faster and more cheaply than an international scientific consortium that embarked on the same task a decade ago. Venter wants to do it by 2001, maybe sooner, and turn an eventual profit from the work.
Skepticism, even derision, greeted these plans when Venter announced them 18 months ago. It couldn't be done, the scientists said. A disastrous business plan, the business people said.
It's too early yet to declare the critics wrong, but the auguries inside Celera Genomics these days are not of disaster.
To the contrary, a rising sense of confidence pervades the place. A warm-up project -- a cooperative endeavor with federally funded researchers to unravel the genes of the fruit fly, an important laboratory organism -- fell a few months behind schedule but now is going well, participants say.
As advisers and employees, Venter has drawn around him two Nobel Prize winners, the former head of the National Cancer Institute, and other stars of medicine and computer technology. Workers are putting finishing touches on a control room at Celera that looks for all the world like the command deck of a starship, complete with overhead screens to monitor every stage of the company's operations. Earlier this month, lab workers cleared fruit-fly genes out of their gene analyzers and began pumping through genetic material from human beings. Celera is moving into high gear.
The company is using a fast technique that shreds all of an organism's genetic material into tiny pieces, analyzes them and then tries to assemble the resulting bits of information into a seamless whole. (Gene-reading machines can handle only a few hundred units of information at a time, out of billions.) The method is controversial because it presents researchers with mind-boggling problems of computer analysis: performing quadrillions of calculations to fit all the little pieces together. The technique has never been proven to work on something as large as the genetic instructions, or "genome," of a human being, which has an estimated 3.5 billion units of information.
Celera's computer experts, who include some of the biggest names in the field known as computational biology, are working furiously to perfect computer routines that can perform the necessary calculations. "Two years ago, there wasn't a computational problem in biology that really stressed the state of technology," said Paul Gilman, director of policy planning for Celera. "Now there is."
To accomplish Celera's goals, Venter has built a striking edifice. The company has installed close to 300 super-fast new gene analyzers, making Celera three times larger than any other gene-sequencing lab in the world. The electric bill alone is $60,000 a month and growing.
The computer cluster Venter is installing will be one of the world's most powerful, comparable to the machines that model nuclear explosions or global climate patterns, according to its designers at Compaq Computer Corp. Celera's computer room will contain 1,200 computer processors known as Alpha chips, the fastest processor on the market. Already, the hard disks attached to Celera's computer would hold the contents of the Library of Congress with room to spare.
It's uncertain how well Celera's chosen analytical technique will work at mapping human genes. But it's clear, nonetheless, that Celera will wind up with an accurate gene map, perhaps by next year. Even if Venter's technique fails to produce a perfect genome, his critics acknowledge, the company could obtain a good gene map by matching partial data from its own analysis with a "rough draft" of the human genome that is due next spring from the publicly funded Human Genome Project.
Given that reality, Wall Street has begun to focus mostly on Celera's financial prospects. Reaching deep into the pockets of a Connecticut company backing his venture, Venter is spending some $410 million to get Celera off the ground, making it one of the priciest biotechnology start-ups in history. The big question for investors is this: With gene information rapidly becoming available for free on public databases, can Celera earn a profit selling it?
Rocking the Scientific World
Celera Genomics is the brainchild of senior executives at a scientific-instrument company in Norwalk, Conn., known as PE Corp. As it was perfecting a super-fast new gene analyzing machine, the company realized that banks of these instruments working together might permit researchers to complete a map of human genes sooner than the 2005 deadline set by the federally funded Human Genome Project.
Medical researchers around the world are so eager to have a completed gene map, which promises to jump-start the battle against cancer, AIDS, Alzheimer's disease and a host of other ailments, that the PE executives thought such a venture might have commercial potential.
Tony White, chief executive of PE Corp., said in an interview that he and his aides considered and rejected several candidates to head the new venture. They kept coming back to one name. Craig Venter, then heading a nonprofit gene research institute in Rockville, had made his reputation as a pioneer of rapid analytical methods.
The executives approached Venter, who was working mainly on mapping the genes of single-celled organisms. "He said, `You guys are certifiable,' " White recalled. " `You're crazy. But I'll come listen.' "
The PE plan proved too audacious for Venter to resist. The announcement of the venture in early 1998 rocked the scientific world. "Celera" is taken from the word celerity, meaning swiftness. Federally funded scientists had already considered and rejected the fast method Venter proposed to use, choosing a technique that was more laborious but virtually certain to work. Now this upstart was threatening to upend all their plans and steal the glory of publishing the first complete map of human genes.
Even as they criticized Venter's proposal as dubious, the federal researchers accelerated their own timetable and promised a "rough draft" gene map by this spring and a final map by 2003, instead of 2005. Both sides have tried to downplay the notion that they are locked in a race, but that is how it looks to the outside world. Indeed, the Venter announcement spurred other companies to pile in, promising gene maps of their own, though none is spending the kind of money Venter is.
The Business of Genetic Information
Unlike federal scientists, who doubted Venter's plans would work at all, executives at other biotechnology companies were fairly sure he could achieve his scientific goals. But they were at a loss as to how he would make money doing it. Bowing to strong pressure in the scientific community, Venter promised to make his raw data public for free. What exactly, other business people asked, did he plan to sell?
To this day, Venter and his aides labor to explain their business plan. Just because they intend to give away raw data on Celera's Web site doesn't mean they are giving away everything of value, they say.
They foresee Celera doing for genetic information what Bloomberg L.P. has done for financial news or the Lexis-Nexis database service has done for general and legal news. The mere existence of public information, they say, does not mean that information is easy to search or easy to put into useful form. They see their future as making genetic information easy to use, giving researchers around the world powerful tools to compare genes, display them and understand their function.
Moreover, the fast technique Venter is using, assuming it works, should produce an exhaustive body of information about the minute genetic differences that underlie the diversity of the human race. Celera executives believe there's a potentially lucrative market for this kind of research as drug companies try to figure out, say, why a drug kills some people but makes others better.
For the first year or so after Venter's announcement, financial analysts weren't sure what to make of Celera. But lately some of them have weighed in. This spring, PE Corp. issued a separate class of stock to track Celera's market value. Celera is bleeding red ink and will be for at least the next few years, but the handful of financial analysts who have looked closely at the venture see profitability by 2002 or 2003.
While warning that an investment in Celera "requires a high degree of scientific understanding, plus a great deal of faith," Bear, Stearns & Co. Inc. said in May that the stock could double over a year to 18 months. It has more than doubled in the four months since the company made that prediction, closing at $39.31 1/4 on Friday. Bear Stearns has maintained a positive rating on the stock, as have other analysts.
"I would say from a Wall Street perspective, the biggest risk here is no longer scientific," said Eric Schmidt, an analyst with S.G. Cowen Securities Corp. "It probably is how soon and how large a business this might be. No one has been able to show in the long term that you can make money selling genomic information. But I firmly believe this is the best company in the genomics sector. The capital and the technology are first-rate."
Despite such sentiments, deep skepticism persists among many biotechnology executives. William Haseltine, chief executive of Human Genome Sciences Inc. in Rockville and a former business associate of Venter's, noted that any venture to sell genetic information will compete with the federal government and the Wellcome Trust, the world's largest charity and a major backer of genetic research.
Moreover, a coalition of pharmaceutical companies has promised to make public a database of genetic diversity, one of the things Venter hopes to sell. And at least three other genetics companies are offering or planning products much like those Venter envisions.
Indeed, PE Corp. has itself warned investors, in filings with the Securities and Exchange Commission, that taking a stake in Celera is a risky proposition. "There is a high degree of uncertainty that Celera Genomics will be able to achieve profitable operations," PE Corp. warned.
Plowing Ahead Toward Profitability?
Inside those buildings off Frederick Road, and at another Celera laboratory in California, worries about long-term profitability are on the back burner. For the moment Celera has more than enough money to pay its bills, and the company's 405 employees are preoccupied with the immediate scientific problem of unraveling the genes of flies and men.
Long term, they're planning to tackle the genes of mice, corn and many other organisms. The new gene analyzers were a little shaky when first deployed, Venter acknowledges, but at this point there's no question they can pump out enormous amounts of information.
Celera already has started signing up customers -- four deals with large pharmaceutical and agricultural companies have been announced, and Venter said more are in the works. In exchange for fees of several million dollars a year, the companies get broad access to Celera's database.
Venter and his ultimate boss, PE chief executive White, readily acknowledge the risks in their business plan. Gene research is moving at such dizzying speed that drug companies still are figuring out how to use the information, both men say, and its ultimate value is anybody's guess. But they have decided to plow ahead in the belief a profitable market will materialize.
"There's an element here of `Field of Dreams,' " White said. " `If you build it, they will come.' "
Every cell of every living organism contains genetic material made up of the compounds adenine, thymine, cytosine and guanine, represented as A, T, C and G. The precise order of these letters regulates every aspect of the organism's life from conception to death. Here is how Celera Genomics is unraveling the 3.5 billion letters of the human genetic code.
1. Sperm and blood cells containing genetic material are collected from volunteer donors.
2. DNA is extracted from cells and chopped up into tiny bits.
3. Billions of copies of each DNA fragment are needed to permit efficient machine analysis. So the fragments are spliced into bacteria that work like living copy machines. Each germ produces billions of offspring, each containing copies of the original DNA fragment.
4. The human DNA is extracted and treated with special dyes that make each unit of genetic information glow a particular color under laser light.
5. Hundreds of machines with robot arms pump DNA fragments into thin glass tubes. The negatively charged DNA is pulled toward a positive charge at the end of each tube. As DNA fragments emerge, a laser beam and camera record the dye color. Scientists now have the sequence for one small DNA fragment.
6. Running quadrillions of calculations, computers match each DNA fragment against every other to find overlapping ends. Ultimately, all fragments are reassembled into a complete genetic sequence.
SOURCE: Celera Genomics
A Who's Who of Celera
Mark Adams, vice president for genome programs, is a leading expert in gene-sequencing technologies and co-discoverer of one particularly fast method.
Peter Barrett, executive vice president and chief business officer, joined Celera from PE Corp., the company in Norwalk, Conn., that is funding Celera's start-up costs.
Samuel Broder, executive vice president and chief medical officer, is the former director of the National Cancer Institute. He was the first scientist to push the idea, in the mid-1980s, that AIDS could be treated.
Anne Deslattes Mays, vice president of software systems, is in charge of building the complex computer programs that will allow Celera to manage and maniuplate huge amounts of genetic data.
Eugene W. Myers, senior director of informatics research, is a star scientist in computational biology. He writes software that assembles millions of pieces of genetic information into a finished map.
Marshall Peterson, senior director of infrastructure technology, is an expert in deploying complex computer systems that must be highly reliable.
Hamilton Smith, senior director of DNA resources, won a Nobel Prize in 1978 for discovering a type of enzyme that permits genetic manipulation. He is regarded as the world's expert at physically manipulating DNA.
J. Craig Venter, president and chief scientific officer, is a pioneer at developing rapid methods of genetic analysis. He has published complete gene maps for more organisms than any other scientist.
CAPTION: It's in the Genes (This graphic was not available)