OVER THE PAST DECADE AND A HALF, scientific discoveries have combined to create entirely new technologies such as genetic engineering and production of synthetic antibodies. Cancer research has been both a source and a recipient of much of this progress. Insights into cell mechanisms and the immune system have ended the search for a "magic bullet" to cure cancer; rather, today's treatments are designed to operate in known ways against known processes.

						What Causes Cancer? Oncogenes Through genetic engineering, the mechanisms by which normal cells become cancerous could be studied. Oncogenes—the hypothesized cancer-causing genes—could actually be identified, and George Todaro and Robert Huebner's oncogene theory expanded to accomodate new theories. It now appears that no matter what the "cause" of cancer—genetic, chemical, viral or some combination thereof—some mechanisms may be the same. Discovery of the First Oncogene While conducting genetic studies in the early 1970s, Peter Duesberg and Hidesaburo Hanafusa discovered that the RNA virus that causes cancer in chickens contains a gene (src) that produces a protein necessary for cancer. Removing that gene prevented the virus from inducing cancer. The researchers had found the first oncogene. Proving the Existence of Human Oncogenes The next step—confirming the existence of human oncogenes—was complicated and involved the work of several research groups. Teams led by Robert Weinberg and Michael Wigler were able to pinpoint the first human oncogene. Since that time, several human oncogenes have been identified. Finding a "Proto-oncogene" Soon after the discovery of an oncogene, Harold Varmus, Michael Bishop and Dominique Stehelin found a gene in seemingly normal chicken and human cells that was similar to the src gene that could induce cancer in chickens. They named it a "proto-oncogene" and suggested that it is present in normal cells of most animals.

		Recombining DNA in Laboratories The new biotechnologies of the early 1970s—recombinant DNA technology, genetic engineering, and hybridoma technology—have spawned a biomedical revolution and a whole new industry. With the capacity to cut, splice, sequence and recombine DNA, the basic material of life, it has become possible to isolate, identify, manipulate, study and modify the action of individual genes—the process of genetic engineering. Two major discoveries in molecular biology were important to the development of recombinant technology. One was restriction enzymes—the "scissors" of genetic engineering with ability to cut DNA at known points. The other was to reverse transcriptase, which allowed sections of DNA to be copied from RNA.

		Hybridoma: A Second Crucial Biotechnology In 1975 biomedical science and oncology took a giant step forward with the introduction by Cesar Milstein and George Kohler of hybridoma technology, in which an earlier cell fusion technique was used to create and mass-produce a special kind of antibody. This antibody, named a "monoclonal antibody," would have an enormous impact on cancer diagnosis and treatment.

		Sequencing DNA In the mid-1970s two methods of sequencing DNA—determining the precise order of nucleotides (AGCT)—were developed and named after their originators: Frederick Sanger (the Sanger procedure) and Allan Maxam and Walter Gilbert (the Maxam-Gilbert procedure). These procedures allowed the study of the action of specific genes.

		Gene Banks and DNA Probes and Atlases Once sequencing methods were developed to establish the order of nucleotides on a strand of DNA, a wide range of inventions followed: DNA probes to fish out genes of known sequences; DNA atlases listing sequences of different genes; and gene banks—central computerized repositories for storing known sequences.

		Another Cancer Frontier: Immunology As advances in genetic engineering allowed investigation at the gene level of mechanisms by which a cell becomes cancerous, the complicated immune system of the human body was charted. Researchers realized that the body itself had a system that could be, and often was, used to fight cancer. A new biotechnology, hybridoma technology, enabled the immune system to be manipulated and enhanced. As more and more is understood about the immune system and the nature of cancer, a vaccine—possibly using antigens to promote immunity—may be feasible.

		Biological: A New Form of Treatment Recombinant DNA technology and hybridoma technology have opened the way to a new form of cancer treatment using biological response modifiers, or "biologicals." Unlike drugs used primarily to poison cancer cells in conventional chemotherapy, biologicals harness the body's defenses. Some, such as monoclonal antibodies, are among the most promising of the "biologicals." As antigens of specific cancers are identified, monoclonal antibodies can be used alone to "tag" such cells for destruction by the immune system, or used as delivery systems for conventional drugs to attack only cancer cells.

		RNA's New Role In 1981, Thomas Cech upended genetic dogma by proving that RNA—ribonucleic acid—can be more than just a genetic messenger. Even though RNA is not a protein, it can cut and splice itself just like an enzyme. In 1983, Sidney Altman demonstrated that such bits of catalytic RNA—ribozymes—can act on other molecules too. Richard Mulligan's experiments in the early 1980s turned retroviruses, which contain RNA, into an important new tool for the burgeoning field of recombination technology. Mulligan gutted a retrovirus of its own RNA (making it noninfectious) and replaced it with custom RNA able to code for specific genes. The custom retrovirus used the enzyme reverse transcriptase to reverse-copy its RNA into a piece of DNA, then spliced the piece into the cell's DNA.

		Viruses and Cancer In 1980 Robert Gallo proved that RNA viruses can cause human cancer with a demonstration that human T-cell leukemia is caused by the virus HTLV-1. A related virus, HTLV-2, was soon isolated from patients with hairy cell leukemia, while a third, HTLV-3 (later known as HIV), would shortly be linked to AIDS. AIDS and cancer research have remained intertwined ever since.
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