X-Message-Number: 11788
From: "Robert Moore" <>
Subject: High-speed evolution in a test tube
Date: Thu, 20 May 1999 04:59:20 PDT

You all on Cryonet are probably way ahead me on this one, but the biotech 
development technique described below was news to me.

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High-speed evolution in a test tube: Biotechnology's new wave

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.

--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.


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