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Body's Cells Mobilized in Novel Fight of Infection

February 07, 1988|DELTHIA RICKS | United Press International

Not since a wayward mold blew into a laboratory window 60 years ago to contaminate a culture dish, accidentally triggering the age of antibiotics, have scientists voiced such excitement over a new class of pharmaceuticals.

Colony stimulating factors--words sometimes spoken in an awe of their dazzling potential--have captured the imagination of medical science as little has since the advent of penicillin. Ultimately, they could become potent biologic weapons in the fight against cancer, infections, radiation sickness, massive burns and possibly even AIDS.

Like antibiotics, colony stimulating factors (CSFs) aid the body in its fight against infection. But CSFs, unlike antibiotics, are derived from the human body itself.

Because the body is an apothecary of disease-fighting capability, potentially more efficient than synthetic antibiotics, scientists who have cracked the DNA codes of the factors believe they are now on the threshold of harnessing nature's own pharmacy.

Avoid Extreme Terms

They have found a way to manipulate production of the immune system's key white cells, those that constitute a surveillance and attack network against infection and disease.

But scientists bite their tongues to avoid terms such as "wonder" or "miracle" when referring to the yet-to-be-approved drugs. Most, like Dr. David Golde, chief of hematology and oncology at the UCLA School of Medicine, spell out their accolades carefully, looking toward a day when CSFs will become therapies of choice.

"I am very optimistic," declared Golde in his lab, where some of the country's most significant developments in gene technology have occurred in recent years. "I think this is one of the biggest advancements since antibiotics."

"They're so new," said cell biologist Peter Ralph in charge of the CSF project at Cetus, an Emeryville, Calif., biotechnology company, "that it might be surprising to most classical drug development people that they work at all."

CSFs are minute hormones--protein molecules--produced naturally by the body in quantities so small their presence sometimes escape detection. But their importance--regulating the type and quantity of blood cells in the circulatory system at all times--far outweighs the paucity of their number.

'Very, Very Potent'

The hormones are responsible for a daily production of billions of blood cells and derive their name from their function--stimulating production of certain "colonies" or groups of cells.

"They're dilute but very, very potent," said molecular biologist Philip Whitcome of the Amgen biotechnology firm in Thousand Oaks, describing the concentration of CSFs in human blood.

"If you drained all of the blood out of your body, you wouldn't have enough of these factors to put on the head of a pin," he said.

Increasing the population of circulating white cells can augment the body's capability to battle infection, the prime motivation for CSF therapies. White cells are also important because of their uncanny locomotion, allowing them to move against the bloodstream or migrate through the walls of capillaries to reach damaged tissue.

While red blood cells, carriers of oxygen, are part of the blood transport system, white blood cells are the passengers in it. When colds or other infections strike, CSFs are the body's first response to invasion, immediately calling on cellular troops to marshal forces against the attack.

Scientists have identified several colony stimulating factors and each is genetically programmed to trigger stem cells deep in the bone marrow--where all blood components are manufactured--to grow and differentiate into specific types of blood cells.

Subject to Replication

But scientists, having deciphered some of the factors' DNA codes, now can genetically engineer them in the lab in mind-boggling quantities, producing CSFs for the series of clinical trials under way to test the hormones' effectiveness in people whose immune systems are suppressed by drugs or disease.

There are four known CSFs that boost production of specific white cell types:

G-CSF is for white cells known as granulocytes and M-CSF is for the white cells called macrophages. GM-CSF stimulates both types of cells and Multi-CSF, also known as interleukin-3, boosts the myeloid group of white cells.

So far, genetically engineered versions of G-CSF and GM-CSF have been tested in human subjects.

"We can now ask questions that never have been asked in medicine," said Golde. "We can ask how high do we want the white count and actually reach that level."

He and Dr. Jerome Groopman of Deaconess Hospital in Boston recently tested CSFs in 16 AIDS patients in whom they attempted to augment immune system components badly ravaged by viruses, bacteria, protozoans and the antibiotics administered to eliminate the infections.

Not Intended as Cure

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