Scientists may have discovered one missing link in the chain of events that cause cancer, for the first time tracing how a free virus may find its way into a cell and transform it into a tumor.
In a single stroke, the finding offers powerful evidence for the idea that some cancers may work by commandeering normal "growth factor" chemicals in the body, and using them to force cells to grow uncontrollably.
Robert Weinberg, a leading cancer gene researcher at the Massachusetts Institute of Technology, described the finding as an important development in the relatively new study of the molecular details of cancer. It is as if scientists, knowing only that a switch turned on a mechanism, have glimpsed the wiring that connects the two.
Scientists have known for some time that since the growth and daily lives of cells are controlled by genes the source of cancer must be genes gone amok.
In the past few years, excitement has been caused by discovery of some 20 genes, mostly in animals, that can cause tumors directly when they are inserted into healthy cells.
These genes are called transforming genes, or oncogenes.
Viruses, which are small seed-like packages of stray genes existing everywhere in the environment, have been found to carry among their stray genetic material some of these oncogenes. The viruses thus can "infect" animals with cancer, a disease not normally counted as an infectious disease.
But the mystery has been how cancer genes turn normal cells into tumorous monsters.
Stuart A. Aaronson of the National Cancer Institute pointed out that one of the barriers in cancer research has been that, although many "cancer genes" have been found, the things they do in the body do not seem related to the obvious signs of cancer in a cell such as uncontrolled growth.
The new discovery shows a clear and direct path between cancer genes and their apparent power to transform normal cells into tumorous ones.
The finding was made simultaneously by two sets of researchers and will be published in two journals, Science and Nature, in the next two weeks.
The discovery came when a chemical, called "platelet-derived growth factor" (PDGF) and which the body uses to trigger some normal cell growth, also was found to be the key element in a cancer-causing virus in monkeys.
The finding has been made in monkey genes, but since humans have virtually identical systems, scientists hope the discovery will lead to more general conclusions about cancer and chemicals that trigger growth.
Scientists Harry N. Antoniades at the Blood Research Institute of Harvard and Michael W. Hunkapillar at California Institute of Technology had found and published the list of amino acids cranked out by genes that make up platelet derived growth factor. This substance is believed to be a chief factor causing muscle and other deep tissue cells in the body to grow back and repair wounds. Protein chemist Russell F. Doolittle of the University of California at San Diego saw the published sequence and cranked the list into his computer to see if there was any other interesting substance with a similar sequence. The computer showed that PDGF was a near-perfect match for a cancer-triggering virus. It is called "Sis," for Simian sarcoma virus.
A theory presented itself at once to the scientists at several institutions who had worked on either PDGF or Sis.
It is believed that the objects called platelets in the bloodstream carry PDGF with them. Platelets are critical to clotting and other parts of healing, and so the platelets congregate at sites of wounded tissue. The platelets break open, and release among other things PDGF to help start the growth of new cells to replace damaged ones.
The PDGF brought to cells is used up during the healing, and cell growth stops once the body is back to normal.
But now it has been discovered that a wild virus also contains the gene to make a sinister copy of PDGF. This virus, it is believed, may be able to cause cancer by mimicking the wound-healing process up to a point.
In this hypothesis, the Simian virus attacks some cells, enters them and inserts the gene for making PDGF.
The cells under the influence of PDGF start dividing and growing, growing and dividing. In the healing process, PDGF is supposed to be present only temporarily during healing.
But when the virus invades, it brings genes that make PDGF without stopping--that is, a mechanism causing cell division and growth, but none to stop the continuing, abnormal production of PDGF. So the growth goes on, presumably creating a tumor.
The researchers who will publish their work in Science magazine include Doolittle, Aaronson, Antoniades, Hunkapillar, Leroy E. Hood of Cal Tech, Keith C. Robbins and Sushilkumar G. Devare of the National Cancer Institute. Those publishing their work in Nature will be Thomas F. Deuel of Washington University School of Medicine and Michael Waterfield of the Imperial Cancer Research Fund in London.