High-speed evolution in a test tube

Gina Miller (echoz@hotmail.com)
Tue, 18 May 1999 13:53:16 PDT

High-speed evolution in a test tube: Biotechnology's new wave By LAURAN NEERGAARD
AP Medical Writer

SEATTLE (AP) - Biotechnology companies are causing a revolution in evolution: conducting high-speed evolution inside test tubes to improve micro-organisms in ways Mother Nature never would, and thus create a range of super-products.

Called "directed evolution," proponents say the process could prove one of the most important steps in biotechnology since genetic engineering.

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 - everything from super laundry detergents to novel drugs.

"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 at a meeting of 5,000 biotechnologists this week, companies outlined numerous others under study - from anticancer drugs and better vaccines to a fade-resistant laundry enzyme that promises to let people wash a red shirt together with underwear and socks without the 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 directed evolution pioneer Frances Arnold of 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 can in days create new super-germs to test new antibiotics.

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

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.

"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 anti-viral drug that has dose-limiting toxicity. Now it is searching for drug companies to work with in improving such drugs.

-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 deactivate dyes released in water, meaning it could prevent a red shirt from staining white laundry.

-Arnold evolved an enzyme to help synthesize antibiotics more cheaply and
with less pollution.

-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, even AIDS. Also under study are anti-cancer drugs and enzymes to strengthen chemotherapy.

Gina "Nanogirl" Miller
Nanotechnology Industries
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