From “Closing In On Cancer: Solving a 5000-Year-Old Mystery” by National Cancer Institute.
ANCIENT EGYPTIANS
3000 B.C. - 800 B.C.
“MIXING MEDICINE AND RELIGION, prescribing pills and pigs' ears, the physicians of Ancient Egypt treated patients for several forms of cancer. Hieroglyphic inscriptions and papyri manuscripts distinguish between benign and malignant tumors, and reveal that surface tumors were removed surgically. For cancers of the stomach and the uterus, compounds of barley, pigs' ears and other ingredients were ordered. Ointments, enemas, castor oil, suppositories, poultices and parts of animals were among commonly dispensed medications” (par. 5).2500 B.C. – 1600 B.C.
“Seven papyri, discovered and deciphered late in the 19th century, provided the first direct knowledge of Egyptian medical practice. Two-known as the "Edwin Smith" and "George Elbers" papyri-contain descriptions of cancer written about 1600 B.C., and are believed to date from sources as early as 2500 B.C. The Smith papyrus describes surgery, while the Ebers' outlines pharmacological, mechanical and magical treatments” (par. 6).
GREECE AND ROME
525 B.C. - 848
“[T]he great doctors Hippocrates and Galen-who would dominate medical thought for 1500 years-lifted medicine out of the realms of magic, superstition and religion, defining disease as a natural process, and basing treatment on observation and experience. Cancers were identified, with warnings against treatment of the more severe forms” (par. 7).
“By the time of Hippocrates, Greek philosophers believed that four elements-earth, air, water and fire-each with its own quality of cold, dry, moist and hot, governed the universe. Harmony derived from balance among the four. Four corresponding fluids, or humors, governed man's health-blood, phlegm, yellow bile and black bile. Illness and disease were the result of imbalance among the four humors” (par. 8).
MIDDLE AGES
1110 - 1478
“From the Dark Ages to the Renaissance, the Roman physician Galen (c.129-200) was the most influential figure in medicine through his writings. Appointed physician to the gladiators of his hometown of Pergamum early in his career, he gained a wealth of anatomical insight treating fractures and brutal wounds. Opinionated and prolific, he produced 500 treatises whose contents were unchallenged for 1500 years” (par. 11).
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| Ninth-century: Charlemagne with Popes Gelasisus I. and Gregory I. |
“The development of hospitals was an outstanding Arab contribution to medicine. . . . While monastic orders built hospitals in the Near East to care for wounded Crusaders, the great hospitals of the Middle Ages were at Baghdad, Damascus and Cairo” (par. 12).
Medieval view of disease: “Sin, Satan, astrology and the ancient Greek theory of the four bodily humors-blood, phlegm, yellow bile and black bile-were variously invoked to explain human illness. Uroscopy charts depicted shades and conditions of urine samples, and indicated what diseases might be the cause. Cancer continued to be explained as the result of an excess of black bile, curable only in its earliest stages” (par. 3).
RENAISSANCE
“WITH THE FALL OF CONSTANTINOPLE, invention of the printing press, and voyages of discovery to the New World, the medieval world ended and the modern world began. In every discipline dogma was discarded, replaced by the humanist spirit of individual dignity and spiritual freedom expressed in such acts as Martin Luther's religious revolt and Paracelsus' burning of the works of Galen. Science and surgery advanced as physicians returned to direct observation of the human body” (par. 5).1517 - 1590
“The theory that cancer was caused by an excess of black bile (one of the so-called four bodily humors: blood, phlegm, yellow bile and black bile) continued to prevail in the 16th century. Cancer was considered incurable, although a wide variety of pastes containing arsenic were compounded to treat its manifestations” (par. 8).
1609 - 1665
“THE FOUNDATIONS OF MODERN SCIENCE were laid in the 17th century. Scientists asked 'how' rathen than "why," aided by the microscope and other new instruments. Galileo's telescope and Newton's laws of gravitation advanced understanding of the physical universe, and William Harvey described the continuous circulation of the blood. With the humoral theory of disease discarded, and cancer no longer attributed to bile, researchers looked for answers elsewhere” (par. 10).
The first cancer surgery is performed in the seventeeth century, but "lack of anesthesia and antiseptic conditions made surgery a risky choice" (par. 7). "A renowned German surgeon, Fabricius Hildanus, removed enlarged lymph nodes in breast cancer operations, made amputations at the thigh, and devised a tourniquet to control bleeding. Johann Scultetus performed total mastectomies, and Marco Severinus' illustrated book on surgical pathology was a landmark in the field" (par. 7). Gaspare Asellie discovers that abnormalities in the lymphatic system could be the primary cause of cancer (pars. 8-9).
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| Robert Hooke's 'Micrographia' (1665) |
1683 - 1687
"A DUTCH EYEGLASS MAKER, Johannes Jansen, and his son Zacharias are credited with inventing the microscope c.1590 and the telescope in 1608. The Jansen microscope was rapidly put to work by 17th-century researchers throughout Europe who investigated the structures and functions of human organs, as well as plant life and bacteria" (par. 1).
Cell discovered: Robert Hooke discovers the cell. "His observation of "cells" leads to the 19th-century theory of the cell as the basic unit of all living organisms" (par. 2).
AGE OF REASON: ONCOLOGY
1733 - 1788
"IDEALS OF POLITICAL AND INTELLECTUAL FREEDOM ignited revolutions on both sides of the Atlantic in the 18th century. . . . Modern pathology was established, and physical diagnosis became more common. With the first systematic experiments in cancer, oncology was born as a medical discipline. Environmental cancers were reported, and hospitals specializing in cancer care were opened" (par. 4).
French physician Claude Gendron (1663-1750) finds that "cancer arises locally as a hard, growing mass, untreatable with drugs, that must be removed with all its 'filaments' (par. 5). Researchers begin to make correlations between "working conditions and the health of workers" and effects of smoking and cancer (par. 6). French scientiss Jean Astruc and chemist Bernard Peyrilhe experimented with diagnosing cancer. John Hunter makes surgery a science. He teaches that if a tumour can be physically moved, it can be surgically removed. If immovable, then the tumour, he suggested, should not be removed due its involvement with other tissues (pars. 6-8).1800 - 1892
"A series of remarkable discoveries in the closing years of the 19th century set the stage for 20th-century research in oncology and biomedical sciences. Cancer research accelerated as Röntgen described X rays, the Curies isolated radium, and Müller observed abnormalities of cancer cells" (par. 9).
- Better microscopes "made possible the examination of cells and cellular activity. Study of cancer tissues and tumors revealed that cancer cells were markedly different in appearance than normal cells of surrounding tissue" (par. 12).
- "Ether anesthesia in general surgery enabled the science of surgery to advance rapidly" (par. 13).
- First cancer statistics collected.
1859 -1929
"Cancer research in cell culture, chemical carcinogens, diagnostic techniques and chemotherapy firmly established oncology as an experimental science" (par. 1).
- Radiotherapy treatment successful (par. 2)
- Theory posits that "cancer was due to abnormal chromosomes" (par. 3).
- New science of chemotherapy encouraged "researchers to continue the pursuit of chemical means to control cancer" (par. 4).
- 1913: "[P]ublication of the first known article on cancer's warning signs in a popular woman's magazine, and formation of a nationwide organization dedicated to public education on cancer (par. 6).
- "Theory became fact in 1915 when experiments confirmed that cancer could be induced by chemicals" (par. 7).
- "[T]he first reliable statistics on the incidence and mortality rates of cancer were compiled (par. 9).
NATIONAL CANCER INSTITUTE (NCI) FOUNDED
1930 - 1950
NCI provided new laboratories for research, encouraged advancements in surgery and chemotherapy research, and focused on early discovery of cancer. "Techniques for diagnosing cancer at earlier stages were developed in the years following World War II, and efforts towards public education increased" (par. 17).
1952 - 1971
- 1953: "James Watson and Francis Crick unveiled their model of the structure of DNA (deoxyribonucleic acid), the cellular material carrying genetic information. The genetic code was soon broken, and many discoveries followed" (par. 1).
- "Cancer researchers discovered much of the new information on cells" (par. 1).
- Chemotherapy treatment successes lead to the NCI's "National Chemotherapy program devoted to testing chemicals that might be effective against cancer" (par. 3).
- "By the late 1970s, some 45 chemicals had been found effective against 29 forms of cancer. After a time, researchers found that combinations of drugs were more effective against cancer than those given singly. Childhood leukemia was one of the first cancers that could be cured in this manner. . . . A four-drug combination developed by Vincent DeVita raised the cure rate of Hodgkin's Disease from nearly hopeless to 80 percent" (par. 5).
- "By the mid-1960s, the inescapable correlation [between smoking and cancer] led the United States Surgeon General to issue a public report on smoking and health (par. 6).
- Environmental pollutants: "A connection seemed possible between the increasing incidence of cancer and industrial pollution of the environment" (par. 7).
- "James and Elizabeth Miller showed that many chemical carcinogens are really pre-carcinogens, able to cause cancer only when metabolized. They are thought to damage DNA, producing cancer-generating errors in the genetic code" (par. 8).
- "Howard Temin and David Baltimore discovered an enzyme, reverse transcriptase, which explained the mechanism by which RNA viruses convert their genetic information into DNA, making genetic engineering possible" (par. 9).
- "Enactment of the National Cancer Act in 1971 created a National Cancer Program administered by the National Cancer Institute. Its Director was to report directly to the President" (par. 10).
1972 - 1981
"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" (par. 3).
- "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" (par. 3)
- "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" (par. 5).
- Cell fusion technique creates a "special kind of antibody. This antibody, named a 'monoclonal antibody,' would have an enormous impact on cancer diagnosis and treatment (par. 7).
- "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" (par. 9).
- New form of cancer treatment discovered involving "biological response modifiers, or 'biologicals'" (par. 10). Biologicals do not destroy cancer cells like chemotherapy treatment, but "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" (par. 10).
- 1981: Thomas Cech proves that RNA (ribonucleic acid) can not only act as a genetic messenger, but it "can cut and splice itself like an enzyme," even though it is not a protein" (par. 10).
- "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" (par. 11).
"BY USING TRANSGENIC ANIMALS, the role of specific cancer-causing oncogenes and tumor progression factors are studied. Researchers have shown that some oncogenes can be moved into specific animal tissues under certain conditions and produce cancer. Other experiments in retrovirus-tagged mutagenesis follow the insertion of a retrovirus near a cell's proto-oncogene to see if the proto-form converts to a cancer-causing oncogene" (par. 1)
1986 -1992
"TECHNIQUES FOR STAINING DNA grew steadily more sophisticated, molecular biology and molecular genetics advanced, and scientists made great leaps in establishing the link between chromosomes, the genes they carry, and cancer. Typically, cancer occurs when a series of damaged genes accumulate in a cell that eventually becomes cancerous" (par. 1).
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| How Proto-oncogenes become Oncogenes |
"Proto-oncogenes are normal genes which can change into their deadly alter-egos, oncogenes. The proto-oncogene bcl-2 (discovered in B-cell lymphomas) prevents cells from dying. The gene's intended role is to prolong the life of "memory" cells in the immune system. When activated inappropriately, bcl-2 allows quantities of white blood cells to accumulate and eventually mutate to produce the cancers known as lymphomas and leukemias" (par. 6).
"As knowledge of the human genome grew, researchers began to focus on the possibilities of gene therapy-replacing defective or missing genes with normal genes. In 1989 NIH researchers performed the first approved gene transfers, inserting foreign genes to track tumor-killing cells in cancer patients. This project proved the safety of gene therapy" (par. 11).
"Researchers removed special immune cells from patients with skin cancer, inserted a gene which boosted the immune cells' production of a natural killing factor, and grew the restructured cells in a laboratory. When reinjected, the immune cells fought the cancer with renewed vigor.
In a Trojan horse assault on brain cancer, Kenneth Culver and Michael Blaese put a gene that confers sensitivity to an antiviral drug into a harmless virus. Then they put the virus into mouse cells, and the mouse cells into a human brain tumor. In the human brain, the mouse cells release viruses, and the viruses invade dividing tumor cells, carrying with them the new gene. The new gene makes the human brain tumor cells susceptible to killing by an antiviral drug" (pars. 13-15).
1992
"POTENTIAL SOLUTIONS TO THE PROBLEM of cancer seem limited only by the imagination. In some promising new therapies, the body's internal weapons are trained on cancerous growths. In other treatments, no less a powerful element than light is employed to eradicate the invaders. Still other research focuses on stopping the tumor's blood supply" (par. 1).
1993 - 1997
"STRATEGIES AIMED AT KEEPING CANCER FROM OCCURRING, progressing or recurring remain invaluable weapons. By the early 1990s, more than forty chemoprevention trials tested the power of assorted vitamins, minerals and drugs against cancer. New fronts in the war against cancer have opened as health care professionals increasingly focus on the special needs of at-risk populations and cancer survivors" (par. 7).
- NCI advises the public that lifestyle choices and cancer are linked. Research "indicates that a third of cancer deaths are linked to diet, and study after study proves that regular exercise offers protection from some kinds of cancer" (par. 8).
- Catching cancer early with screenings increase the chances of successful treatment.
- Research reveals that people should limit their exposure to "everyday carcinogens" (par. 9).
- The possibility of creating a cancer immunization vaccine becomes possible due to successful research in creating immune system stimulants.
- "Laser capture microdissection is a new technique that allows researchers to capture tumor cells in seconds, while the cell still expresses genes as it would inside the body" (par. 11).
- "By 1996 the p53 tumor suppressor gene and the powerful protein it encodes emerged as the darling of the biochemical world. Mutated or crippled versions of p53 had been implicated in 52 human cancers. Thousands of scientists have focused their research on this gene, hoping to use p53 as a tool for early diagnosis; as a guideline for varying treatment of cancer patients with disabled copies of p53 and those with working copies; and as a method of tracking a tumor back to its origin-the corruption of a cell by a specific carcinogen" (par. 12).
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