May 17, 1999

Scientists Speed Up 'Evolution'

By The Associated Press

SEATTLE (AP) -- It's a revolution in evolution that Charles Darwin never dreamed of: Biotechnology companies are conducting high-speed evolution in test tubes to create everything from super laundry detergents to novel drugs.

Called directed evolution, the process could prove one of the most important steps in biotechnology since genetic engineering. It's getting a lot of attention at a meeting of 5,000 biotechnologists this week in Seattle.

The idea is to discover in nature substances that perform in a certain way but have drawbacks -- like a cancer-fighting protein that can only be used in small doses because of side effects -- and force them to rapidly evolve to be better.

"It's optimizing the best nature can provide," explained Jay Short, president of Diversa Inc., which is trying to improve blood transfusions with the process.

The first commercial product derived from directed evolution is an enzyme that fights tough laundry stains better than a previous detergent ingredient. But companies are studying dozens of others -- from anticancer drugs and better vaccines to a fade-resistant laundry enzyme that promises to let people wash a red shirt together with underwear without their socks turning pink.

In biotechnology, the process until now has been: ``Here are genes from nature, and what can I do to squash these into a workable commercial product?" said Russell Howard, president of Maxygen Inc., a leader in the field.

But redesigning genes or the proteins they produce to fit a specific need is very difficult and expensive because scientists simply don't understand enough about how these complex substances work, said Frances Arnold, a directed evolution pioneer at the California Institute of Technology.

Nature pressures species to adapt, forcing diversification and survival of the fittest.

With directed evolution, biotechnologists use various laboratory methods to pressure genes to mutate in thousands of ways, doing in days or weeks what can take nature years. It took decades for certain bacteria to evolve to resist antibiotics, for instance, but companies in days can create new super-germs to test new antibiotics.

Sometimes they cause mutations that nature never would, creating enzymes that can withstand mixing with strong chemicals or boiling temperatures, for instance.

Then, in a high-tech twist on how farmers breed better animals and plants, scientists can pick the most promising newly evolved genes and combine them into even better "daughter genes" that produce new drugs or biochemicals.

"We're breeding at the molecular level," explained Arnold, who says the industry is investing heavily in directed evolution.

"If you don't use this technology, then you're at the whim of trying to find an enzyme in nature that does what you want," added Glenn Nedwin, president of Novo Nordisk Biotech, maker of that evolved detergent ingredient.

In the pipeline:

--Diversa is evolving enzymes to strip certain molecules from blood, thus converting Type A and Type B blood donations into the Type O blood that almost everyone can use.

--A recent Maxygen experiment suggests it could improve by a stunning 200,000-fold the potency of alpha interferon, an important cancer and antiviral drug that forces doctors to limit doses because of toxicity.

--Maxygen recently received $20 million in government funding for directed evolution, mostly to create better vaccines for the military.

--Moving faster are biochemicals. Novo Nordisk has evolved an enzyme found in mushrooms to inactivate dyes released in water -- something that could prevent a red shirt from staining white laundry.

--Arnold evolved an enzyme to help synthesize antibiotics more inexpensively and with less pollution. And Diversa is finalizing an enzyme to make chicken feed manufacturing cheaper and less polluting, because makers would no longer have to add phosphate.

--University of Illinois scientists just reported a way to evolve certain immune system cells to better fight autoimmune diseases in which the body attacks itself -- even AIDS. Also under study are anti-cancer drugs and enzymes to strengthen chemotherapy.

Here are links:
My Home Page

Contact address - please send e-mail to the following address: