History of Oncology

The history of oncology is at least as interesting and instructive as the history of other clinical disciplines with strong basic sciences. Because oncology enrolls multiple, separate specialties of medicine it is broader in perspective than many other disciplines. The recent influx of money for research and development has enriched the discipline in more ways than finance, for the fundamental goal of the "war on cancer" and the war chest was to acquire enough information to formulate therapies and strategies to eradicate this pestilence. This fund of knowledge is extraordinary now and growing. The molecular details of many cancer pathways are understood. This generates so much excitement and enthusiasm in persons in the field that very short shrift is given to history. Sometimes to the detriment of the field, for those who do not learn their history often as not find themselves repeating it. So let us talk about history. Partly for the value in it and partly for the enjoyment of it.

Surgery is the oldest known method of curing cancer. The Egyptians of the Middle Kingdom knew about surgery and cancer. We have the Edwin Smith papyrus circa 1600 BCE in which a case of breast cancer is discussed, with the counsel not to do incision and drainage, for the problem is not infection but a different process not amenable to that. Further it seems to advise that the process is too far advanced for surgical cure of what it is–that being presumably breast cancer. I am quite sure about the latter inference but not so confident about the former. Aside from the Edwin Smith and similar records which are few but which seem to have been composed by experienced practitioners of the healing art there are the legends and myths of Egypt and Mesopotamia. They hint at medical and surgical skills but are more difficult to interpret. The example that first comes to mind is the Egyptian version of the Hebrew bible story of the brothers Cain and Abel. The characters are two divine couples who are half brothers married to full sisters. So we have Seth and Osiris married to Nepthys and Isis. Seth had the southern half of Egypt and Osiris had the northern half (Lower Egypt). Seth wanted more and tricked his brother, trapping him in a box and drowning him in the sea. The faithful and determined spouse, Isis, retrieved the box and her husband’s dead body and took him to the god Thoth for resurrection. Seth meanwhile heard of the planned procedure and stole the corpse to dispose of his brother again. This time he dismembered the corpse and hid the parts all over the land of Egypt, fourteen pieces in all hidden in that many locations. But the indefatigable and resourceful Isis retrieved the pieces, approximating them and wrapping the whole in purple cloth. The tale includes a strange detail, too, for we are told that everything but the penis was located by Isis. This is the fundamental guide to the kings and pharaonic court as to details of proper mummification and hoped for resurrection. An even more strange detail of the story is how Isis impregnated herself with the help of Thoth to have her son Horus. The god Thoth extracted the essence of Osiris (semen?) and, even though the body had been dismembered and even though Osiris was indubitably dead, there was conception. You ask whom Horus favored–Osiris or Thoth. Well, remember how Thoth is depicted by the Egyptians. (He is the Ibis headed god of Egypt.) It would have been obvious if Thoth were the father. The story is long and has even more strange twists and turns. In the end Horus captures his uncle Seth and brings him before the judgement seat of Ra who in turn leaves sentencing to Horus and Isis the aggrieved parties. Horus proceeds to lop heads until he gets to Seth himself. Isis cannot see her brother killed and stops Horus who then lops his mother’s head off. But the skillful Thoth reattaches Isis’s head and she is resurrected. If you are interested in this story or the original, and much older story from Mesopotamia (Ishtar and her beloved Tammuz), I refer you to the linguist and author Zecharia Sitchin whose style is lively and whose interpretations are fresh and challenging.

Modern cancer surgery progressed from inauspicious beginnings in rural America to present day state-of-the-art proven effective surgical science. From the first successful removal of an abdominal tumor in frontier America by Dr. Ephraim MacDowell (the patient Mrs. Jane Crawford survived three decades after her ten kilogram ovarian mass was resected) to the first codified practice of cancer surgery by Dr. William Halstead and the first radical hysterectomy by Dr. Ernst Wertheim took only one century. Anesthesia, blood transfusion (and now promised blood replacement products that may make transfusion of other people’s blood much less common), and antibiotics have rewritten the course of surgical history. For surgical oncology the advent of the controlled clinical trial has made more difference than any other advance. We now know the effect of what we do. And we can test one regimen against another. Short of clinical applied chaos theory, this is as good as it gets. We can test the best combination of factors or therapies. Test neoadjuvant chemotherapy or preoperative radiation therapy with or without neoadjuvant chemotherapy. These adjuvant modalities have their own supportive programs, too. The use of specific cytokines to make the marrow reserves produce more red or white cells accomplish what anesthesia and blood banking do for surgery–extend the usefulness and enhance the safety of the program. We are entering a new era of cancer therapy where surgery is more judicious, safer, and more effective for cure. Although some cancer sites still resist the surgeons curative attack (pancreas cancer, upper biliary tree cancer) progress continues.

Radiation therapy has a colorful history, too. You probably think there is no history prior to Dr. Wilhelm Conrad Röntgen. No, here one has ancient legend and myth, too. I refer you to the story of Inanna (one of the twelve great gods of Sumer and Akkadia, granddaughter of their highest god, Anu, and one of the most fascinating characters of all literature) and her death and resurrection by Enki, son of Anu and brother of Enlil. I quote Dr. Sitchin in his new book "The Cosmic Code" published by Avon Books, 1998, ISBN 0 380 80157 4.

Upon the corpse, hung from the stake,

They directed the Pulser and the Emitter.

Upon the flesh that had been smitten,

Sixty times the Food of Life,

Sixty times the Water of Life,

They sprinkled upon it;

And Inanna arose.

He is translating extant cuneiform text. He goes on to add that the use of radiation (the Pulser and the Emitter) are depicted in a surviving cylinder seal from the region. To call this interesting is to understate the situation hugely. The clay tablets are exceedingly old. The ancients were not supposed to have had technology like this at their disposal. Perhaps they had unusually keen imaginations. (But it is hard to imagine rustics imagining high technology.)

Modern radiation therapy derives from work on the xray by Röntgen and discovery of the natural forms of radioactivity by Marie and Pierre Curie and Antoine-Henri Becquerel. Within a decade of discovery of intense radiation emitters, the rays were tested against many disease processes. Sometimes the disease responded but worse complications set in later. This is the conundrum in which the treatment is worse than the disease itself. Cancer is one of those situations where few things will do worse things to the patient than the disease itself, so investigations of the efficacy and best use radiation in cancer treatment proceeded. In three decades of use quite a bit of fundamental knowledge was acquired and some superficial cancers were curable by xray while accessible cancers were curable by radium therapy. Our knowledge has exploded since then. The support of modern physics, radiobiology, dosimetry (the science of measuring, computing, calculating, and optimizing the dose of radiation) and collaboration with surgeons and medical oncologists have made modern radiation therapy a recognized effective method of cancer cure. The specialty is now called radiation oncology. Newest advances in this specialty have to do with fractionation (how the dose is given in time) and high dose rate brachytherapy treatment. In addition enhancement of effect by the addition of chemotherapy is practical now. Much of oncology is now multimodality treatment. Good timing and support of the patient while receiving these sometimes toxic regimens are critical and are the subject of clinical trials.

Chemotherapy is the newest mode of cancer cure. While common cancers are still most often cured by surgery or radiation or a combination of them, some less common cancers are amenable to chemotherapy cure. The basic science of pharmacology and a knowledge of cell kinetics and the cell cycle dependence of some agents allows modeling of treatment and optimization of a chemotherapeutic regimen. Toxicity of the agents can be mollified in some cases, especially in the case of bone marrow suppression. Very high dose treatment with rescue by bone marrow transplant or peripheral stem cells is a working technology. Antibiotics and a knowledge of immune suppression are supportive of these efforts. The incurable can be cured in some situations. The frontiers of cancer therapy are being pushed ever further forward.

Biologic manipulations are on the horizon. Take some tumor tissue from patient with incurable malignant melanoma. Extract the patient’s own natural killer cells from the tumors. Clone great numbers of these cells. Enhance them with substances that will make them even more able to kill cancer cells (tumor necrosis factor producing genes inserted into the nuclei of the natural killer cells). Infuse these cells by the billions back into the patient. See what happens. This is not science fiction, although it sounds like it. (Not from the Sumerian tablets, either, although it does sound like it.) This is being done. At the National Cancer Institute. By our premier surgical oncologist. This is opening the door to the future. More on this later in the NEWS section.

History leads into present and future in cancer medicine. I will put together a list of reading materials if there is any interest.

http://www.cancerdoc.com/History.htm

Neoplasia is typical of many words used in the oncology lexicon. It is rooted in Greek and means new growth. It is not specifically cancer, for unless specified as malignant, the new growth may lack capacity to metastasize (spread to distant sites by blood vascular or lymphatic channels) and therefore be benign. Certain body sites make benign lesions (our word for something wrong with the body) tantamount to malignant ones, implying lethality. An example is the intracranial space which does not accommodate growing lesions well so that enlarging benign growths can and do prove lethal even though they often lack the hallmarks of malignancy. A neoplasm is characterized by its location, local extensions, microscopic appearance and presence or absence of spread to regional lymph nodes. If the lesion is malignant (a decision made by the pathologist examining cytology or histology specimens, meaning cells obtained by fine needle aspiration biopsy or tissue obtained by core needle biopsy or open surgical biopsy), there is more characterization to be done of the lesion as well as a generalized search for spread to distant and to regional sites. Each primary cancer (named in accordance with the anatomical site of origin) has a certain pattern of spread that is typical. This helps with the search by hinting strongly where to look. Prostate cancer spreads to the adjacent seminal vesicles, the regional pelvic lymph node, and the bones. Colon cancer spreads to the mesenteric lymph nodes and to the liver. Lung cancer spreads in a characteristic pattern, too. One can even guess to which side of the neck and supraclavicular space the cancer cells will go–according to the pattern of flow of the lymph fluid. In this way lesions low in the right lung will have a likelihood of ending up in the opposite left side of the neck and supraclavicular space. And those high in the right lung will end up to the right side of the trachea and in the right neck and supraclavicular space. Not only the staging of cancer but also the expectant surgical and radiotherapeutic management of cancer are helped by knowledge of anatomic and physiologic factors bearing upon cancer spread. Even simple cancers like basal cell cancer of the skin obey certain laws of nature. Those arising near the embryonic fusion plane where the nose meets the "cheek" have access to routes of spread that carry the cells deep into the face where they can grow undetected after partial and ineffectual removal only to recur extensively years later. This knowledge of cancer behavior is as much knowing what the body will allow, encourage, or block, as what the cancer cells themselves are programmed to do. This body of knowledge is termed clinical oncology. A practitioners fund of knowledge increased with each new and instructive patient, each well written and studied paper, each new and definitive textbook. But most of all the instruction is by caring for patients and applying skills refined through years of practice of oncology.

Cancer is the second leading cause of death in the United States. Half of all men and one-third of all women in the US will develop cancer during their lifetimes. Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking and eating a better diet. The sooner a cancer is found and treatment begins, the better are the chances for living for many years.

Oldest Descriptions of Cancer

Cancer has afflicted humans throughout recorded history. It is no surprise that from the dawn of history doctors have written about cancer. Some of the earliest evidence of cancer is found among fossilized bone tumors, human mummies in ancient Egypt, and ancient manuscripts. Bone remains of mummies have revealed growths suggestive of the bone cancer, osteosarcoma. In other cases, bony skull destruction as seen in cancer of the head and neck has been found.

Our oldest description of cancer (although the term cancer was not used) was discovered in Egypt and dates back to approximately 1600 B.C. The Edwin Smith Papyrus, or writing, describes 8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."

Origin of the Word Cancer

The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 B.C.), considered the "Father of Medicine." Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab. Carcinoma is the most common type of cancer.

Renaissance Period

During the Renaissance, beginning in the 15th century, scientists in Italy developed a greater understanding of the human body. Scientists such as Galileo and Newton began to use the scientific method, which later began to be used to study disease. Autopsies, performed by Harvey (1628), allowed an understanding of the circulation of blood through the heart and body that had remained a mystery.

In 1761, Giovanni Morgagni of Padua was the first to do something considered routine today. He performed autopsies to relate the patient's illness to the pathologic findings after death. This laid the foundation for scientific oncology, the study of cancer.

The famous Scottish surgeon John Hunter (1728-1793) suggested that some cancers might be cured by surgery and described how the surgeon might decide which cancers to operate on. If the tumor had not invaded nearby tissue and was "moveable," he said, "There is no impropriety in removing it."

A century later the development of anesthesia allowed surgery to flourish and the classic cancer operations such as radical mastectomy were developed.

Nineteenth Century

The 19th century saw the birth of scientific oncology with the discovery and use of the modern microscope. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer. As Morgagni had correlated the autopsy findings observed with the unaided eye with the clinical course of illness, so Virchow correlated the microscopic pathology.

This method not only allowed a better understanding of the damage cancer had done to a patient but also laid the foundation for the development of cancer surgery. Body tissues removed by the surgeon could now be examined and a precise diagnosis made. In addition, the pathologist could tell the surgeon whether the operation had completely removed the tumor.

Cancer Causes

From the earliest times, physicians have wondered about the cause of cancer. The Egyptians blamed cancers on the Gods.

Humoral Theory: Hippocrates believed that the body contained 4 humors (body fluids) - blood, phlegm, yellow bile, and black bile. A balance of these fluids resulted in a state of health. Any excesses or deficiencies caused disease. An excess of black bile collecting in various body sites was thought to cause cancer. This theory of cancer was passed on by the Romans and was embraced by the influential doctor Galen's medical teaching, which remained the unchallenged standard through the Middle Ages for over 1300 years. During this period, the study of the body, including autopsies, was prohibited for religious reasons, thus limiting knowledge.

Lymph Theory: Among theories that replaced the humoral theory of cancer was cancer's formation by another fluid, lymph. Life was believed to consist of continuous and appropriate movement of the fluid parts through solids. Of all the fluids, the most important were blood and lymph. Stahl and Hofman theorized that cancer was composed of fermenting and degenerating lymph varying in density, acidity, and alkalinity. The lymph theory gained rapid support. John Hunter (1723-1792) agreed that tumors grow from lymph constantly thrown out by the blood.

Blastema Theory: In 1838, German pathologist Johannes Muller demonstrated that cancer is made up of cells and not lymph, but he was of the opinion that cancer cells did not arise from normal cells. Muller proposed that cancer cells arose from budding elements (blastema) between normal tissues. His student, Rudolph Virchow (1821-1902), the famous German pathologist, determined that all cells, including cancer cells, are derived from other cells.

Chronic Irritation: Virchow proposed that chronic irritation was the cause of cancer, but he falsely believed that cancers "spread like a liquid." A German surgeon, Karl Thiersch, showed that cancers metastasize through the spread of malignant cells and not through some unidentified fluid.

Trauma: Despite advances in the understanding of cancer, from the late 1800s until the 1920s, cancer was thought by some to be caused by trauma. This belief was maintained despite the failure to cause cancer in experimental animals by injury.

Parasite Theory: In the 17th and 18th centuries, some believed that cancer was contagious. In fact, the first cancer hospital in France was forced to move from the city in 1779 because of the fear of the spread of cancer throughout the city.

A Nobel Prize was wrongly awarded in 1926 for scientific research documenting stomach cancer being caused by a certain worm. With the inability to confirm this research, scientists lost interest in the parasite theory.

Modern Day Carcinogens

More recently, other causes of cancer were discovered and documented. In 1911 Peyton Rous, at the Rockefeller Institute in New York, described a sarcoma in chickens caused by what later became known as the Rous sarcoma virus. He was awarded the Nobel Prize for that work in 1968 .In 1915 cancer was induced in laboratory animals for the first time by a chemical, coal tar, applied to rabbit skin at Tokyo University. One hundred and fifty years had passed since the most destructive source of chemical carcinogens known to man, tobacco, was first identified in London by the astute clinician John Hill. It was to be many years until tobacco was "rediscovered" as a carcinogen.