The New York Times - October 7, 1986
Harold M. Schmeck Jr.

The discovery of the factor, interleukin 3, solves a scientific puzzle that has persisted for several years and offers a potential new strategy for treatment of many medical conditions in which a patient's blood production and immune defenses are seriously impaired. Cancer and AIDS could be among the targets of medical use of the newly discovered substance.

The researchers, scientists at Genetics Institute, a biotechnology company in Cambridge, Mass., report in the Oct. 10 issue of the journal Cell that they discovered the gene for the factor as well as the substance itself. This knowledge makes it possible to grow the blood growth factor in bacteria and animal cells to provide supplies for intensive study. They are beginning studies of the factor's effects in animals and hope to start testing it in humans about a year from now.

No Human Use Currently

Dr. Steven C. Clark, a leader of the research, said his group hopes to begin clinical trials sometime late next year.

The first medical uses the scientists will test will be speeding patients' recovery from bone marrow transplants, correcting the blood-destroying side effects of radiation and chemotherapy in cancer patients and attempting to restore immune defenses in patients with acquired immune deficiency syndrome.

Dr. Clark and other scientists at the company stress that interleukin 3 is not available for any use in humans at present.

Dr. Robert Kamen, research vice president of Genetics Institute, said the company was concentrating on developing products to stimulate the activity of the normal blood-forming and immune defense systems. Human interleukin 3, also known as multicolony stimulating factor, was discovered in the course of this research.

Bone Marrow's Complex System

The co-leader of the research group on interleukin 3 is Dr. Yu-Chung Yang. Other members are Agnes B. Ciarletta, Patricia A. Temple, Margaret P. Chung, Sharlotte Kovacic, JoAnn S. Witek-Giannotti, Anne C. Leary, Ronald Kriz, Robert E. Donahue and Gordon G. Wong.

Many serious illnesses result from failure of some aspect of the blood-forming and immune defense systems. These failures can occur either as a fundamental part of the disease process, as with AIDS, which destroys the body's ability to fight disease, or as an unwanted effect of treatment, such as when anticancer drugs or radiation destroys blood and immune defense cells.

The ultimate source of all cells of blood and the immune system is the bone marrow, but the way the fundamental marrow cells give rise to all of these many different specialized cells is complex and only partly understood.

Much of the research toward understanding this natural process of regulation in humans began with studies in laboratory animals of how blood formation is controlled. The natural control substances that have been found have often been named colony stimulating factors because they stimulate the growth of colonies of specific cell types in the laboratory.

Substance Found in Mice

The best known of these factors has been interleukin 2, which is already in experimental use in cancer treatment.

Others include macrophage colony stimulating factor and granulocyte stimulating factor. Both stimulate the body's production of large quantities of special immune defensive cells, and both were found in mice and in humans.

Interleukin 3, however, could not be found at all in human tissues. In the mouse, this substance was important as a stimulator of cells that developed early in the progression of cell types that arose from the bone marrow. It was capable of causing repopulation of virtually all types of the animals' blood cells after they had been destroyed by massive radiation or the equivalent.

Why no comparable growth factor could be found in human cells was a puzzle, Dr. Clark said. Some scientists thought that the factor had been lost through evolution and that its function had been replaced by something else.

Good Luck With Gibbon Apes

He and his colleagues found the human equivalent partly by good luck, he said. They found a substance in the white blood cells of gibbon apes that acted as a powerful stimulator of blood cell production. After long and painstaking study of this substance and purification of its gene, they conducted a computer search for similar genes in other species. The computer matched it with interleukin 3 of mice, even though the match between the DNA subunits of the two species' genes amounted to only 47 percent.

Then the scientists searched a library of human DNA sequences for something comparable to the gibbon gene. The result, Dr. Clark said, was the identification of the human gene, whose sequence of DNA subunits showed a 99 percent match with the gibbon gene.

Dr. Clark said using the mouse gene as a probe, the means tried in earlier efforts, had apparently failed to find the human gene because the two had diverged to an unusual extent in the evolution of the two species.

"What makes this both exciting scientifically and important is that we now have DNA probes for all of the known colony stimulating factors," said Dr. Clark. Now, he said, it should be possible to use them to systematically look for yet other substances that may play roles in the complex regulation and production of blood and defense cells.

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