White Potato, Red Potato
As in nature, however, evolution in the lab can be a bumpy ride. Some researchers caution that the new technique has its limitations. “You’re not going to turn a potato into a broccoli,” says Arnold at Caltech. “Maybe you can turn a white potato into a red potato. The question is, what’s close, in terms of evolution? We just don’t know yet.”
It’s a question lacking easy answers. At Maxygen, company president Simba Gill says DNA shuffling has worked in 90 percent of experiments-and the firm drops the experiments that fail. Duke University biochemist Homme Hellinga says he would like to see chemists combine aspects of rational protein design and directed evolution, using computers to model new proteins and then testing well they can adapt to different environments.
But even proteins that evolve beautifully in the lab face classic development hurdles, warns Arnold. When Arnold’s lab evolved a detergent enzyme for Procter and Gamble, the new enzyme passed lab tests with flying colors-only to fall apart inside company washing machines. “You can’t mimic a washing machine in a high-throughput screen,” Arnold says. “You eventually have to try it.” In the same way, she adds, companies such as Diversa and Maxygen will have to prove that each of their evolved molecules works in the real world.
Yet another obstacle could crop up in an arena that is becoming central to almost all of high technology these days: intellectual property. Both Maxygen and Diversa have staked relatively broad patent claims, which some industry observers say might not survive litigation. And a patent issued to AME in 1998, if broadly interpreted, might force some players in the field to seek licenses from AME in order to continue their projects. AME set up a licensing program this spring and has already successfully defended its patent against one challenge in Japan. Regardless of how the legal landscape shapes up, though, directed evolution seems certain to offer researchers in academia and industry alike a faster route to better proteins for years to come.
CompanyYear of IPO,
Dollars RaisedClaim to FameMajor PartnersApplied Molecular Evolution
San Diego, Calif.2000,
88 millionTeaching old medicines new tricksMedImmuneDiversa
San Diego, Calif. 1999,
174 millionImproving on nature’s extremesDow Chemical, Novartis, AventisEnchira Biotechnology
The Woodlands, Texas 1993*,
16 millionA new push toward pharmaceuticalsGenencorMaxygen
Redwood City, Calif.1999,
96 millionMolecular breedingNovo Nordisk, DuPont/Pioneer Hi-Bred, AstraZenecaNovo Nordisk Biotech
Davis, Calif.–R&D subsidiary of Novo Nordisk, the world’s largest maker of industrial enzymesMaxygen, UC-Davis