The Woodlands, about 40 kilometers north of downtown Houston, is one of those planned communities that endeavors to provide virtually anything its residents might desire in an idyllic suburban setting. Among the Woodlands’ five villages are bike paths and hiking trails, parks and golf courses, a shopping mall of Lone-Star-State proportions and an arts pavilion, not to mention a hospital, schools-and what may be the world’s single largest genetically-engineered-mouse facility.While the mice are not part of the careful plans of the community developers, they are key to the future of a local biotech company called Lexicon Genetics. Lexicon was founded six years ago by Arthur Sands and Allan Bradley, who were both at the Baylor College of Medicine at the time. Bradley is now director of the Sanger Centre in Cambridge, England, the largest European contributor to the Human Genome Project, while Sands stayed behind in Texas to run Lexicon and to tackle what he and Bradley assumed-rightly-would become the single most pressing issue in biology: Once the human genome is sequenced, what happens next? How is that copious information-the sequences of those 30,000 to 40,000 genes-transformed into medical therapies that will improve the lot of humankind?
“The genome encodes all potential drug targets for the pharmaceutical industry for all time,” says Sands. “It’s all there, encoded in the genes, which make proteins, which are the targets for drug discovery. Now we have the sequences. The big questions are, what do these genes do, and how do you mine the most valuable genes out of the genome for drug discovery?”
Lexicon’s answer is mice: 300,000 of them. Specifically, “knock-out” mice, in which a single gene has been targeted and disabled. Biologists have used such mice for over a decade to illuminate the functions of genes by studying how the mice develop without them. Lexicon, however, has managed to industrialize and automate the knock-out production process, rolling out the high-tech mice the way Detroit does automobiles. What once took months, Lexicon can now do in hours. The company is presently churning out 1,500 such genetically compromised mice a week, which is why it’s building its $40 million Woodlands mouse facility, the size of a few football fields, to hold them all.
It’s this kind of massive, grand-scale effort that could represent the future of drug discovery in the postgenome world. In the same way that it took an automated, factory-like effort to sequence the human genome in the first place, biologists are now automating some of their favorite research tools-from mice to fruit flies to worms-to make sense of the mountain of new information. This biology at warp speed is, in effect, the mission of the science that has become known as “functional genomics.” And for pharmaceutical companies facing the challenge of turning genomic information into actual drugs, functional-genomics tools are some of the hottest commodities around. To get their hands on as many of these tools as possible, drug firms are partnering with a number of biotech companies that, like Lexicon, promise to help unravel the genome’s mysteries.