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Glowing chickens bring hope in fight against cancer
By CHARLIE EMRICH
Sacramento Bee

 

August 21, 2006
Monday


Take a chicken, add a pinch of jellyfish DNA, and you'll not only get a slightly fluorescent bird, but also one that's likely to play an important role in the development of cancer treatment.

The creation of the glow-in-the-dark chicken, described in June in the journal Nature, explained a new method used to easily modify the DNA of chickens.

While cool in a creepy, mad-scientist sort of way, making chickens fluorescent won't cure cancer by itself. But when combined with earlier research methods, it could transform chickens into small, inexpensive laboratories for the production of cancer-fighting human antibodies.

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The earlier research methods, published by Burlingame-based Origen Therapeutics, already showed that genetically modified chickens can lay eggs that contain human antibodies, specialized proteins the body uses to recognize and fight disease. Such proteins are now being used as drugs to treat challenging diseases such as cancer.

Current cancer-fighting methods such as chemotherapy and radiation kill fast-growing cancer cells as well as any other quickly growing cells, like those that produce hair - making life miserable for patients.

"One of the problems with modern drugs is that they're not very specific," said Dr. Joseph Tuscano of the University of California-Davis Cancer Center. "Even aspirin is not very specific."

Antibodies, on the other hand are "highly, highly specific," Tuscano said, meaning that, like an archer's arrow, they can effectively target a disease.

Antibody-based therapies are one of the biggest advances in cancer treatment in the last 40 years, Tuscano said.

Antibodies are Y-shaped proteins made by the body's immune system that can recognize foreign objects such as viruses by tightly binding to their surface. The top end of the "Y" binds itself to its target, and the other end acts like a flag that signals the immune system to destroy the foreign object.

Unfortunately, this doesn't work very well with cancer cells, which begin as normal, healthy cells and thus are experts at evading detection by the immune system.

Modern technology, however, allows scientists to artificially make antibodies that bridge the gap between the body's ability to find cancer and to fight it.

The new study, which pairs university scientists with Origen Therapeutics and was reported in Nature, describes how the researchers captured certain special cells from an egg, grew and modified them in a lab, and then squirted them back into another egg.

The special cells are known as primordial germ cells, or PGCs, and are found only in embryos, according to university geneticist Mary Delany, who co-authored the study.

A freshly laid chicken egg contains a chick embryo that's about 25 hours old, slightly larger than the head of a pin, and quickly developing just inside the yolk. The PGCs grow outside the embryo until the embryo's heart starts beating. At this point, the PGCs begin a journey into the embryo through the newly formed bloodstream.

It's during this journey that researchers crack the egg and use a very thin needle to take blood from the tiny embryo. If their timing is right, the blood will contain the precious PGCs.

Once the cells are drawn out of the chick embryo, they are grown on their own, or cultured - a difficult task, said Marie-Cecile van de Lavoir, senior scientist at Origen and lead author of the study.

In fact, prior to van de Lavoir's project, no other researchers were known to be successful at capturing and growing PGCs.

"Nobody thought that these cells could be cultured," she said, "but sometimes you get lucky."

One of the problems with culturing and modifying cells like PGCs is that the DNA in the cells can become abnormal. The UC Davis group's contribution was making sure the cells stayed in tip-top condition.

Once cultured, the PGCs are ready for new DNA - in this case, the DNA for a fluorescent jellyfish protein - and are then put back into an embryo.

"You take your cells and load them up into a needle and reinject them," said Robert J. Etches, vice president of research at Origen.

Once reinjected into another embryo, the PGCs develop into the reproductive cells of the chick. When the chick matures and reproduces, the protein can then be harvested from the eggs.

The fluorescence in the chick embryos allows researchers to visually verify the success of their genetic modification.

The jellyfish protein is a common tool for biologists who perform genetic modification studies because its eerie green glow tells them what's worked and what hasn't.

Etches says the promise of the glowing bird is that it offers a cheaper and easier way to grow the important human antibodies that fight killer diseases.

Current methods for producing human antibodies use large batches of costly and complicated cell cultures from the ovaries of Chinese hamsters. The largest factory using this method will be Genentech's soon-to-be expanded production facility in Vacaville, said company spokeswoman Kelli Wilder. There, Genentech manufactures two successful therapeutic antibodies for fighting cancer, Herceptin for breast cancer and rituximab for lymphoma.

Using chickens instead of huge factory tanks of cells promises to simplify and reduce the cost of producing therapeutic antibodies. As Etches says, "You just collect the eggs, separate the yolk from the white, and purify the (antibody)."

 

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