A Glimpse into the Historical Journey of How We Came to Understand Cancer
Just like any other branch of pathology, our understanding of cancer has also evolved over the period of our existence. The earliest recognition of cancer can be seen in fossils of dinosaurs that existed 80 million years ago. More recently though, in around 3000 BC, the Edwin Smith Papyrus has been viewed as the earliest description of cancer. Eight cases of breast cancer were described in this document, and the disease was claimed to have no treatment.
In 1600 BC, we can find attempts that were made to cure cancer. A tool called the “fire drill” was used to remove superficial lesions, whereas cancers of the stomach were treated with a mixture of boiled barley and dates, and cancers of the uterus were treated with an introduction of pigs’ brain and fresh dates into the vagina.
The word “cancer” itself came into existence much later. Hippocrates, who is considered as the “Father of Medicine”, described various kinds of cancers, tagging them with the Greek word carcinos. According to the Humoral Theory of Medicine proposed by Hippocrates, the body consists of four fluids: yellow bile, black bile, phlegm and blood. Disease was thought to be caused by an imbalance of these fluids. Cancer, in particular, was thought to be caused by an excess of black bile.
The Roman physician Celsus (28 – 50 BC) translated the word carcinos to the Latin word cancer. Both words literally meant “crab”, which was the description of the appearance of the veins when a tumor was cut open. Later on, Galen (in the 2nd century AD) referred to benign tumors as oncos (Greek for swelling) and malignant tumors as carcinomas. Galen also believed that consuming an unhealthy diet and bad climate were the main risk factors for cancer. The word “oncologist” is used to describe a doctor who is a specialist in the treatment of cancer in the modern world, and it has been derived from the Greek word oncos that Galen had proposed.
In 657 AD, a prominent Byzantine physician, Paul of Aegina, proposed that cancers of the uterus and breast were most common. He also added that while surgery was futile for uterine cancers, it was beneficial in cases of cancers of the breast. In 1190, Moses Maimonides explained that large tumors should be excised along with its surroundings to the point where healthy tissues are apparent. However, the exceptions to this treatment modality included tumors containing extensive vascular networks, or those located close to vital organs.
One of the earliest examples of an epidemiological study can be credited to Bernardino Ramazzini, an Italian physician whose other works included the use of cinchona bark (from where the drug quinidine is derived) for the treatment of malaria. Ramazzini, in 1713, observed that cervical cancer was hardly seen in nuns, and breast cancer was far more common in this group of people. This eventually paved way for understanding the hormonal influences in various cancers.
As our understanding of cancer pathogenesis evolved, many other theories came into prominence. One theory suggested that breast cancer was the result of milk clots in the mammary ducts. Another theory proposed that acidic lymph was the causative agent behind cancer. Nicolaes Tulp, a Dutch surgeon, believed that cancer was a poison that was contagious. In the 18th century, John Hill was the first to recognise the harmful effects of tobacco.
In 1775, Sir Percivall Pott (an English surgeon) observed that chimney sweeps were associated with scrotal cancer. This was followed by further studies demonstrating other occupation-related cancers. Four years later, in 1779, the first cancer hospital was built in Reims (France). In his 1829 treatise Recherches sur le traitement du cancer, Joseph Récamier (a French gynecologist) described the spread of cancer as metastasis.
In 1838, Johannes Muller, a German pathologist, demonstrated that cancer was made from cells, instead of lymph. His Blastema theory explained that cancer cells developed from undifferentiated tissue that was present between normal cells. Virchow, a student of Muller, proposed that cancer was the result of chronic irritation that “spread like a liquid”.
The first pyloric (1878) and esophageal (1872) resections of cancers were performed by a German surgeon Theodore Billroth. After analysing 1000 autopsy records of women with breast cancer, an English surgeon Steven Paget proposed his “seed and soil” theory of cancer in 1889. He explained that the pattern of metastasis was not random, and appropriate compatibility was necessary between the seed (tumor cells) and the soil (specific tissues) for metastasis to take place. The following year, William Stewart Halsted performed the radical mastectomy to treat breast cancer.
The discovery of X-rays in 1895 by Wilhelm Conrad Rontgen made the detection of tumors non-invasive. Four years later, Tage Sjogren became the first physician to treat cancer with X-rays.
In 1914, German biologist Theodor Boveri presented the Somatic Mutation Theory of Cancer. He believed that a cancerous tumor began from a single cell that began to divide uncontrollably. He further suggested that this carcinogenesis was caused by radiation, physical or chemical insults, or microbial pathogens. The year 1915 saw the induction of cancer in laboratory animals for the first time. These experiments conducted in Tokyo University made use of coal tar to induce skin cancer in rats.
The first successful first successful single-stage total pneumonectomy for the removal of a lung tumor was performed by Evarts Ambrose Graham and Jacob Jesse Singer in 1933. Dr. Graham was a well-renowned American surgeon of his time, and this procedure further raised his stature. Ironically though, he himself died of lung cancer 25 years later.
In 1939, Charles Brendon Huggins demonstrated that hormones were necessary for the growth of certain cancers, thus laying the foundation of further research in this field. In 1946, Louis Goodman discovered the effectiveness of nitrogen mustard in the treatment of cancer at Yale. He later published a paper reporting the use of nitrogen mustard for the treatment of leukemias, lymphosarcoma and Hodgkin’s disease.
Howard Temim, a US geneticist who won the Nobel Prize in Physiology or Medicine (1975), proposed the DNA Provirus Hypothesis of cancer in 1960. This hypothesis asserted the role of certain RNA viruses in the pathogenesis of cancer.
In 1976, Harold Varmus and Michael Bishop discovered the first cellular oncogene, src. Ten years later, American physician and scientist Stephen Friend along with his colleagues isolated the first tumor suppressor gene, Rb. The year 1995 saw the construction of the the first DNA microarray chip. These gene chips are now being researched upon for the development of more individualised cancer treatment regimens.
To conclude, our understanding and approach to the treatment of cancer has witnessed an obvious metamorphosis over the period of several thousand years. While a lot of research has already gone into the disease, one is compelled to believe that the future holds several more tales waiting to be told. And hence we await these enchanting revelations that are destined to unfold in the near future.
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