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From the Head of a Rooster to a Smiling Face Near You
By ALICIA AULT

Published: December 23, 2003


It starts with a chicken, not an egg.

The red combs of roosters and hens turn out to be some of the best
sources for the sugar molecule hyaluronan, a compound that some
doctors are calling the next big thing after Botox.

It is already used to protect the eye during surgery, reduce
inflammation in arthritic knees and prevent postsurgery scar tissue.
Most recently, hyaluronan has become known as the latest treatment for
plumping up facial wrinkles
Hyaluronan, formerly known as hyaluronic acid, may have many more
applications, researchers and doctors hope, as they search for ways to
harness its potential to manipulate cells.

Hyaluronan was discovered in 1934 by Karl Meyer in an ophthalmology
lab at Columbia University. Meyer found the substance in cows' eyes
and determined that it helped the eye retain its shape. The substance
was very viscous, leading Meyer to suspect that it might have some
the****utic use.

But extracting cows' eyeballs was neither appetizing nor feasible
commercially. Along came Dr. Endre Balazs, a Hungarian scientist who
also ended up at Columbia. Using Meyer's procedures, Dr. Balazs
figured out in the early 1940's how to extract and purify hyaluronan
from rooster combs.

The combs were already known "as one of the world's richest sources of
hyaluronan," said Dr. Vincent Hascall, a researcher at the Cleveland
Clinic Foundation who has studied the molecule. And the combs are
plentiful, Dr. Hascall noted, because they are usually thrown away
after slaughter.
In roosters, the comb, essentially a big flap of skin, swells with
hyaluronan in response to testosterone, Dr. Hascall said. Hens have
hyaluronan in their combs, too, but not as much.

In humans and other mammals, the compound is primarily found in
connective tissue, in the eyes, the umbilical cord and in joint fluid,
where it acts like a cushion.

Since the 1970's, hyaluronan has been injected into the arthritic
knees of racehorses to reduce inflammation, and it is used in
veterinary eye surgery.
But the compound was not used on humans until 1980, after Dr. Balazs
sold his patents and methods to Pharmacia, the Swedish drug company.
That year, Pharmacia introduced Healon, a product used in cataract
surgery to protect the cornea while a new lens is installed.

Healon is now owned by Pfizer, but the hyaluronan continues to be
produced in Sweden, building on Dr. Balazs's method.

Pfizer has selectively bred roosters to have superhuge combs. At one
point, the combs grew too big, said Dr. Rolf Bergman, a professor of
physical chemistry at Uppsala University, north of Stockholm, who
helps oversee the hyaluronan operation.

"We stopped getting it bigger and bigger because all of the sudden the
rooster couldn't keep his head up," Dr. Bergman said.
Pfizer rigorously cares for its Swedish white leghorns, in keeping
with Swedish ethics laws, he said.

Plus, fine care makes for a better product. "If the roosters are doing
well," he said, "we get a higher quality hyaluronan."
To extract the product, Pfizer and another major manufacturer,
Genzyme, follow essentially the same process.

Genzyme, of Cambridge, Mass., starts with garden variety chickens from
Northeastern farms. The combs are removed after slaughter (the
chickens are sold for food), frozen and shipped to the manufacturing
plant. Freezing helps destroy bacteria. But when the combs arrive at
the plant, they are raised to room temperature and sliced into chips.
The chips are dumped in a huge vat where they are washed to remove
remaining bacteria, feathers, blood or other contaminants.

At Genzyme, about 1,300 pounds of combs are processed in a single vat.
The vat is drained, and water is pumped in. Hyaluronan is water
soluble, so it leaches into the water.

The water-hyaluronan solution is pumped into a clean tank and
neutralized. The liquid is put through a series of filters to strain
viruses, bacteria and proteins, and then it is pumped into another
tank. Alcohol is added to form a slurry that can be dried into the
final product, powdered hyaluronan.