Designer detergent cleans up

Tired of grey knickers and pink socks?
A new enzyme derived from a toadstool is going to revolutionise your wash

Sanjida O'Connell / London Independent 5jan01

We've all experienced it, the tyranny of the single red sock that sneaks into the laundry basket and dyes an entire load of underwear and white T-shirts a delicate shade of pink. Now a company in the United States can put an end to those dirty greys and hateful pinks; it has created an enzyme originally derived from a toadstool which promises to eradicate stray dyes when washing coloured items. What is new about this potential detergent is not so much what it does, but how it was made: it was designed as a result of an evolutionary development which used the basic principles of Charles Darwin's natural selection.

Unlike normal evolution, however, there is an end point. The scientists are literally watching evolution take place and steering it in the direction they want it to go. Currently many new drugs are produced through rational design: scientists determine what kind of molecular structure they are looking for, and search for it or try to create it from natural products.

Many large companies have had teams of researchers working on rational design for years without a great deal of success. It is a difficult task determining the structure of a chemical to begin with, let alone then having to create a brand new protein and work out how it should fit together to perform the task it has been set.

About seven years ago, three post-doctoral students with little experience in rational design got together and, in less than a year, they had made a product which was a commercial success for Novo Nordisk, one of the largest biotech firms in the business. Pim Stemmer, one of those post-docs and now the Vice-President of research and development at Maxygen, a biotech company in California, has patented his technique of evolving drugs. He calls it "molecular breeding" and likens it to the way in which humans have bred many different kinds of dogs. The difference is that Maxygen is merely breeding molecules.

For great sex you need three things: mutation, recombination and repetition. When an organism makes copies of its genes, errors sometimes occur, random mutations in the genetic code. Usually these are deleterious, but occasionally they can confer new, advantageous properties. Maxygen introduces mutations by making many copies of the genetic material – DNA – that will encode for a particular protein. The new, mutated genes are then inserted into an organism, such as a yeast or a bacterium, and allowed to control the creation of a new enzyme. This enzyme is tested to see if it is any more resistant to salt, temperature, acidity, and so on. Several of these mutant enzymes may show some of the characteristics the scientists are looking for; in the case of the new detergent, they wanted enzymes that could withstand the high temperature and harsh chemical environment of a washing machine.

Each of these enzymes might have been produced by genes which had several mutants, but only one mutant is the useful one. The other mutations could be neutral or disadvantageous. The genes are then recombined – they are broken up and mixed with each other in every possible combination, to simulate the genetic mixing of sexual reproduction, when half the genes from a male are combined with half the genes from a female.

"You've allowed yourself to separate the good from the bad mutations," says Joel Cherry, from the Californian based Novozymes, Maxygen's partner in Molecular Breeding. "That's what's so great about sex."

The other great thing about sex is the repetition. The genes are recombined over and over again, and each new enzyme that is produced is tested. "The more cycles you have, the better it works," says Cherry. In larger organisms it would be the equivalent of individual animals becoming better suited to their environment. In the case of the enzymes, better adapted to life in a washing machine.

It is a faster and more efficient process than trying to find enzymes to do the right job in the natural world. "There are no washing machines in the field packed full of microbes," says Cherry, "Organisms don't grow at 95C." Stemmer gives the example of a gene which, in a few thousand cycles over the course of three weeks, showed a 32,000-fold improvement.

Most of the initial genetic material comes from microbes and other organisms found around the area in which Novozymes and Maxygen work. Their genetic library runs to hundreds of thousands of different kinds of genes. Diversa, another California-based biotech company, concentrates on finding unusual natural microbes, sending people to scour the globe for bacteria – from the skin of a beached and rotting whale, for instance.

Novozymes, one of the biggest producers of enzymes, uses them to create the stone-wash effect in jeans, to soften leather and fabrics and to make high-fructose corn syrup, as well as detergent and the enzyme, a "heme peroxidase" from the ink-cap toadstool, which will prevent those stray red socks causing chaos.

Maxygen is involved in similar areas; the company bred subtilisin, an enzyme that removes stains from clothes and is worth $4-5m. But they have also branched out to agriculture and health. They created a new chemical to treat cancer through chemotherapy, and an enzyme to be used in the manufacture of penicillin.

Currently the company is working on a vaccine against HIV and its work on viral vectors for gene therapy was published last August in Nature. This is where a defective gene or genes, which might cause Parkinson's disease for instance, can be "corrected" by inserting a fully functioning gene. Making viral vectors that insert these genes is difficult but Maxygen has made one that is a hundred times better than existing vectors.

Evolving enzymes is expensive though. "We are often competing against chemical processes and these processes are not very green," says Stemmer. "It's more environmentally friendly to use enzymes rather than solvents." Cherry is more optimistic: he believes people will want industry to adopt manufacturing processes that are potentially more environmentally friendly. "Molecular Breeding will change the future of the biotech industry. It's a powerful way of making enzymes so it's an incredible force for change," he says. And it's an evolutionary force that has existed ever since life on Earth began more than 3 billion years ago.