meline with regard to Cancer’s relationship with Humankind
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5000 BC – Leukemia in Neolithic Woman
In 2015, researchers found what is believed to be the oldest known case of cancer in humans. The cancer, leukemia, was identified in the skeletal remains of a woman who lived near present-day Stuttgart-Mühlhausen (Germany).1
3000 BC – Signs of Cancer
Signs of cancer are found on the bones of mummies from ancient Egypt and Peru dating back as far as 3000 BC. 2
The Edwin Smith Papyrus, which is the oldest written description of cancer known to exist, describes eight cases of breast tumors or ulcers in Egypt that were treated with cauterization. However, the document also states that there is no treatment for cancer. The original document, written in 3000 BC, was acquired in 1862 by Edwin Smith at Luxor, Egypt.345
Known today as the father of medicine, proposed the Humoral Theory of Medicine, which states that the body is composed of four fluids, or humors: blood, phlegm, yellow bile, and black bile. Any imbalance of these fluids was thought to cause disease. He attributed cancer to an excess of black bile. Hippocrates was the first to use the words “carcinos” and “carcinoma” to describe tumors, and hence the term “cancer” was coined. “Cancer” is derived from the Greek word “karkinos,” or crab, which is thought to reference the appearance of blood vessels on tumors resembling a crab’s claws reaching out. He believed that it was best to leave cancer alone because those who got treatment didn’t survive as long.345
168 – Early Cancer Theory
Galen was a Roman physician and a believer in the Humoral Theory of Medicine proposed by Hippocrates. He believed cancer to be curable in early stages, and that advanced tumors should be operated upon either by cutting around the affected area or by cauterization. Galen thought unhealthy diet and bad climate were directly connected to cancer.67
Paul of Aegina was one of the most prominent Byzantine physicians He wrote a seven volume Epitome of Medicine. In his opinion, cancer of the breast and uterus were the most common. In the sixth book of the Epitome, exclusively to do with surgery, he asserted that surgery on uterine cancer was useless. For breast cancer, he recommended removal as opposed to cauterization.68
Moses Maimonides was a prominent physician, scientist, and philosopher, wrote ten medical treatises. His fifth treatise contains surgical aphorisms, some of which pertain to his treatment of cancer. His treatment of large tumors, as he wrote, involves “excis[ing] the tumor and uproots the entire tumor and its surroundings up to the point of healthy tissue, except if the tumor contains large vessels & [or] the tumor happens to be situated in close proximity to any major organ, excision is dangerous.”69
Ramazzini noticed the virtual absence of cervical cancer among nuns, and the high incidence of breast cancer within the same population. He concluded that this difference must be due to their different lifestyle, namely their abstinence. This observation lead the way to discovering the importance of hormonal factors in cancer. His work is a very early example of an epidemiological study. He is also known as the ‘father’ of occupational health for authoring his most well known work – De Morbis Artificum Diatriba (Diseases of Workers).4
John Hunter was a supporter of Stahl and Hofman’s lymph theory of cancer; cancer is composed of fermenting lymph of differing pH and density. He believed that cancers could be removed if they had not yet spread to nearby tissues.6
1761 – Tobacco and Cancer
Giovanni Morgagni began performing autopsies to relate illness to pathological findings,. This helped to set a foundation for the study of cancer.
Percival Pott showed that chimney sweeps had an occupation-related cancer risk. Soot that collected under their scrotum was associated with scrotal cancer. This discovery lead to additional studies which identified other occupational cancer risks. The identification of these risks allowed public health measures to be taken.611
1829 – Metastasis First Recognized
Joseph Claude Anthelm Recamier recognizes the spread of cancer, he coins the term metastasis. The Greeks used the term metastasis to mean “removal from one place to another.”
This is an important finding because it is now estimated that metastasis causes about 90% of all cancer deaths.6
1838 – Cancer is Made of Cells
Johannes Muller, a German pathologist, published ¿ber den feineren Bau und die Formen der krankhaften Geschw¿lste (On the Nature and Structural Characteristics of Cancer, and of Those Morbid Growths Which May Be Confounded with It), which began to establish pathological histology as an independent branch of science. He demonstrated that cancer is made up of cells, although he thought that cancer cells arose from abnormal cells. He believed that cancer cells came from ‘blastema’ (the undifferentiated tissue from which it was believed that cells arose from) between normal tissues.612
The first description of malignant cells in the sputum was reported by W.H. Washe. 13Sputum tests are now performed to screen for lung cancer.
1863 – Cellular Pathology Created
Rudolf Virchow was a student of Muller’. He wrote several papers and a three volume work, Die Krankhaften Geschw Lste, on malignant tumors. He theorized that tumors were the result of chronic irritation and that cancer spread in a manner similar to liquid.612
1878 – A Cancer Treatment First
German surgeon Theodore Billroth performs the first pyloric resection (surgical removal of part or all of the stomach) to treat stomach cancer. Billroth was also the first (in 1872) to remove an esophagus as a cancer treatment.614
1881 – Gastroscope Invented
The first gastroscope, an instrument inserted down the esophagus and used to view and detect cancer in the lower esophagus and stomach, was created by Jan Mikulicz-Radecki.15
1889 – Seed and Soil Theory
Stephen Paget proposed his “seed and soil” theory of cancer. He analyzed over 1000 autopsy records of women who had breast cancer and found that the patterns of metastasis were not random. Thus, he proposed that tumor cells (the seeds) have a specific affinity for specific organs (the soil), and metastasis would only result if the seed and soil were compatible.1617
1890 – The First Mastectomy
William Stewart Halsted, who was the first Professor of Surgery at Johns Hopkins, Harvard, and Yale, performed the first radical mastectomy (removal of the entire breast, the muscles in the front of the chest, and the lymphatic system of the breast) to treat breast cancer.1819
1894 – Cytoscope Invented
The first cystoscope, an instrument that is inserted through the urethra and used to detect cancer of the bladder, was created by Maximilian Carl Friedrich Nitze. 20
1895 – Discovery of X-rays
Wilhelm Conrad Roentgen discovers x-rays. This discovery is thought of as one of the greatest technological accomplishments of all time. It made a huge impact on cancer detection and treatment.
Four years later (1899) Tage Anton Ultimus Sjogren successfully treats cancer with x-rays.6
The newly discovered X-ray radiograph, or Roentgen picture (named after its discoverer, Wilhelm Conrad Röntgen), was used by Franz Konig, a German surgeon to picture an amputated leg which was determined to contain a sarcoma of the tibia.2122The X-ray quickly became a tool for visualizing and diagnosing tumors inside the body. In 1901, Röntgen won the Nobel Prize in Physics for his work on X-rays.
1897 – Bronchoscopy
Bronchoscopy was introduced by Gustav Killian when he removed a piece of pork bone from the bronchus of a farmer. Inspired by his report, Chevalier Jackson constructed the first bronchoscope soon after.2324
The first electrocardiogram (ECG or EKG) reading was taken by Willem Einthoven using a string galvanometer that he designed himself.25ECGs can be used to diagnose some cases of kidney (renal) cancer.
A primitive form of intravenous/excretory urography, a procedure used to visualize the upper urinary tract (by injection of contrast material) and diagnose cancer of the bladder, was developed by Fritz Voelcker and Alexander von Lichtenberg.26
1910 – Viral Theory of Cancer
Francis Peyton Rous provides scientific backing to the Viral Theory of Cancer by injecting chickens with cell free liquids obtained from chicken sarcomas and observing the formation of sarcomas in the injected hens. The virus is named Rous sarcoma virus.
This was the first demonstration of an oncogenic virus and would lead to the discovery of the first oncogene, src.
The human papillomavirus is now considered to be the underlying cause of cervical cancer in humans.27
1914 – Mutation Theory of Cancer
Theodor Boveri proposes the Somatic Mutation Theory of Cancer. He believed that cancer was caused by abnormal chromosomes.
Boveri was on to something when he proposed this theory. It is now known that many things lead to the development of cancer, but genetic instability is at the root of cancer.27
Cancer is induced in laboratory animals for the first time at Tokyo University, by applying coal tar onto the skin of rabbits, leading the way for current cancer research methods. This forever changed the way cancer is studied.6
1924 – Colposcope Invented
The first colposcope, and instrument that is inserted into the vagina and used to view and detect cancer of the vagina and cervix, was created by Hans Peter Hinselmann.28
1927 – First Arteriogram Performed
The first human arteriogram was performed by Egaz Moniz, who developed arteriography, in part, to localize cerebral tumors.29
The use of x-rays for diagnostic examination of the breast was introduced in by Stafford Warren. His technique involved the patient lying on her side with her arm raised and having the picture taken from the side.30
1933 – A Cancer Treatment First
Evarts Ambrose Graham and Jacob Jesse Singer successfully remove a lung from a patient with lung cancer. This was the first time a patient underwent a one-stage pneumonectomy (removal of part of or entire lung) and survived. The accomplishment cemented Graham’s place in history.627
1939 – Hormones and Cancer
Charles Brendon Huggins discovers hormones are necessary for the growth of certain cancers through his research on androgen levels and prostate cancer in dogs. This lays the groundwork for hormone therapy for certain cancers.3132
1941 – Pap Smear Introduced
The Pap smear was introduced as a method of diagnosing carcinomas in the female genital tract by George Papanicolaou.33
Ultrasound imaging was used for the first time for medical diagnostics, specifically the identification of intracranial tumors, by Karl and Friederich Dussik. 34
1945 – Urinary Cytology Used
Urinary cytology, the examination of cells and other materials in urine, was used by George N. Papinicolaou and Victor F. Marshall to diagnose cancer of the bladder. 35
1946 – Discovery of Chemotherapy
Louis Goodman discovers nitrogen mustards can be used in the treatment of cancer. Goodman studied chemical warfare agents during WWII and published a paper reporting the use of nitrogen mustards as the first chemotherapeutic agents against Hodgkin’s Disease, lymphosarcoma, and leukemias.36
1951 – Mammogram Created
An early version of the mammogram, comprised of a cone and compression pad apparatus was created by Raul Leborgne to X-ray the breasts. In the paper reporting the device and its use on several patients, he recommends that “roentgen study should now be included in the diagnosis of mammary pathology.” 37
1960 – Bone Scintigraphy Performed
Bone scintigraphy, or photoscanning of the bone with a radioactive isotope, using Sr was performed as a diagnostic test for spinal metastases by Gynning et al. 38
The Fecal Occult Blood Test (FOBT) detects blood in feces. The blood is shed into the colon when feces passes by cancers lining the colon or anus. The test, is used to screen for colon, rectal and intestinal cancers. It is also able to detect some stomach (gastric) cancers. Often, the blood is not visible to the eye – it is hidden or ‘occult’ – giving the test its name. The test was developed by Dr. David Greegor.39
1968 – First ERCP Performed
The first endoscopic retrograde cholangio-pancreatography (ERCP), an endoscopic procedure used to diagnose cancer in the bile ducts and pancreas, was performed by Dr. William McCune. 40
Retrograde colonoscopy of the entire colon was successfully administered by Dr. William Wolff and his associates.41
Dr. Judah Folkman publishes a paper proposing angiogenesis plays a major role in cancer development. Folkman thought preventing angiogenesis could inhibit tumor growth by starving the tumor of vital nutrients. This theory was originally disregarded by most in the field, but is now fully accepted.
The first naturally occurring angiogenesis inhibitor, thrombospondin, was identified in 1989 by Dr. Noel Bouck. Two more natural inhibitors were discovered by Dr. Michael O’Reilly in Folkman’s lab, angiostatin in 1994 and endostatin in 1997.4243
1971 – Nixon Declares War on Cancer
President Richard Nixon declares War on Cancer by introducing the National Cancer Act. He says the following during his 1971 State of the Union.
“I will also ask for an appropriation of an extra $100 million to launch an intensive campaign to find a cure for cancer, and I will ask later for whatever additional funds can effectively be used. The time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease. Let us make a total national commitment to achieve this goal.”4445
1971 – Radioimmunoassay Created
A radioimmunoassay made to detect alpha-fetoprotein, a tumor marker often found in higher concentrations in those with liver and testicular cancer, was created for screening purposes by Ruoslahti and Seppala.46
The computerized tomography (CT) scan was created by Godfrey Hounsfield. CT utilizes X-rays and computer assisted analysis to generate images that represent ‘slices’ or cross-sections through the target organ(s). CT scans are used to diagnose several different cancers. 47
1973 – Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is based on signals obtained from different tissue types when they are subjected to a strong magnetic field. The signals are used to create digital images of the body. MRI is used to diagnose several different cancers and many other medical conditions. They were developed by Paul Lauterbur and Peter Mansfield. 4748In 2003 the developers won the Nobel prize in medicine for their work.49
The first human positron emission tomography (PET) scanner, an instrument which creates high resolution computerized images was built by Michael Phelps and Ed Hoffman. PET imaging is based on the detection of radiation that is released from chemicals introduced into the body. CT and MRI create good images of anatomical structures they do not provide information about the biological activity (i.e. cell growth) of the imaged area.
PET provides information about the biochemical activity of the observed structures. This allows for the discrimination between objects that are non-living such as a scar from growing cells such as those in a tumor.50
1976 – Harold E. Varmus and J. Michael Bishop discovers the first cellular oncogene, src. This is the same gene carried by the virusoriginally described by Peyton Rous.
Prostate-specific antigen (PSA) is a protein produced and secreted by prostate cells. The protein is a tumor marker that is frequently be found at higher concentrations in the blood of those with prostate cancer. It was created as a possible diagnostic method for prostate cancer by Kuriyama et al.53 The use of PSA tests to screen normal men for prostate cancer is controversial for several reasons. Some prostate cancers do not produce the protein and would be missed. PSA levels can also increase in the blood when cancer is not present (i.e. as a response to infection or inflammation). Patients with elevated levels of PSA under these circumstances could be subjected to unnecessary medical tests and stress.
Robert Bast and his laboratory developed an antibody-based test (immunoassay) to detect a protein that can be detected in the serum of human blood. The protein – cancer antigen 125 or CA-125 – is found at increased levels in the blood of some women who have ovarian cancer.54The test is used to help diagnose some types of ovarian cancers. It is also used to track the progress of treatment and recurrence of the disease.
Detection of human papillomavirus (HPV) DNA in cervical cells as a screening tool for cervical cancer was introduced by Ritter et al.55 The test is very sensitive, and can find infections that would be missed by Pap smears.
1993 – Sonohysterography
In this technique, fluid is used to expand the uterus and an ultrasound probe is inserted into the vagina. Sonohysterography is used in diagnosis of cancer of the endometrium and uterus, and was developed by Drs. Parsons and Lense. 56
1995 – First DNA Microarray Chip
The DNA microarray chip is constructed to measure gene expression levels in plants.
This technology has been advanced and is now used to study cancer in humans. Currently ‘gene chips’ are being investigated as tools in the development of individualized treatment plans.57
1999 – Creation of Tumor Cells
Human epithelial and fibroblast cells are transformed into tumor cells for the first time in a laboratory. This was accomplished by the coexpression of telomerase (hTERT), the simian virus 40 large-T oncoprotein, and an oncogenic allele of H-RAS.58
2003 – The Human Genome Project
The Human Genome Project is completed. The project, started in 1990, identified all the 20,000 – 25,000 genes in human DNA and determined the sequences of the 3 billion chemical base pairs that make up human DNA.
2006 – HPV Vaccine Approved
The first cancer vaccine was approved to prevent cervical cancer
2006 – First Cancer Vaccine