Cancer is not a new disease. It was identified in the bones of prehistoric men and women or in mummies. Reports of breast cancer could be found in Egyptian papyrus. Up to the nineteenth century, it was considered a form of slow-growing torpid infection. Metastasis has been described only in the early 1800s. Cancer became a research topic at the end of nineteenth century, when it was separated from chronic infections, since no germs were found in deep-seated cancer.
On the eve of World War I, national rivalries sprung among European scientists. Pasteur is the symbol of French genius and Koch that of German rigor. They fought, with vigor, and participated in scientific wars at international meetings.
Perceiving the human body as a battleground allows, on the one hand, identification of germs as invaders. On the other hand, there was the defensive immune system to fend off the attacks of the invaders. In other words, there was the fight of the French against the Germans or the British.
This way of thinking has led to real progress with the discovery of vaccines, which boost the immune system or the antibiotics, which help fight the invaders. The immune system with the good and the bad cells is only a way to perceive reality. The immune cells, whose function is to detect and eliminate foreign elements, can also attack the joints in rheumatoid arthritis or the lungs in sarcoidosis. To hide the limitations of this approach, the word “autoimmune disease” has been created. In this frame of mind, cancer is a form of fifth column, whereby it acts like a clandestine group working within patient’s body to attack and sabotage the healthy cells. Cancer cells appear clever enough as to escape attack, to hide from the immune cells that want to protect us. Some cells that are becoming cancerous prefer to commit suicide (apoptosis) rather than attack healthy cells of our sacred body.
In the war setting at the dawn of the twentieth century, a dogma arose. Cancer cells should be killed. The advent of radiation therapy, which kills without discernment good and bad cells led to the eradication of some of localized cancers. Treatment with higher energy beams was a consequence of World War II. Being excluded from the last developments of the Project Manhattan (leading to the first atomic bomb), the Canadians designed independently the first radioactive Cobalt 60 device. The photons were powerful enough to reach deep-seated tumors. The modern linear accelerators, invented in the early 1970’s are a consequence of the invention of the radars. Progress in the death industry sometimes leads to pacifistic, life saving inventions.
The survivors of the gas attacks during World War I, experienced persistent low white blood cells and platelets counts. This led to the use of chemotherapy just after World War II. Here again it took time for a good idea to be applied. The discovery of the modern drugs is a consequence of the military program of World War II. These drugs are still in use today.
The first chemotherapy patient, JD is an acronym that has long identified in the medical literature. He has no name, no date of birth, or no medical record number. P. Christakis has recently unearthed JD's history, a man born in Poland in 1894. He lived in Connecticut and worked in a ball bearing factory until he became ill at the age of 46 in August 1940. What began as enlargement of the tonsils and right submandibular (below the jaw) pain rapidly progressed to multiple enlarging masses that were biopsied and found to be lymphosarcomas, a rare form of cancer. Before long, they occupied the entire right side of his neck, and he could barely open his mouth. He was referred to the Yale Medical Center in February 1941 for X-ray therapy and admitted to what is now Yale-New Haven Hospital. He underwent external beam radiation for 16 consecutive days with considerable reduction in tumor size and amelioration of his symptoms. However, his improvement was short-lived, and by June 1941, he required additional surgery to remove cervical tumors. He underwent several more cycles of radiation to reduce the size of the tumors, but by the end of the year they became unresponsive and had spread to the maxilla. By August 1942, two years after the initial onset of symptoms, he suffered from respiratory distress, difficulty and pain in swallowing, and weight loss, and his prognosis appeared hopeless.
JD’s physicians believed that nitrogen mustard, a related compound of the poison gases responsible for 1,205,655 non-fatal casualties and 91,198 deaths during the war, was his only chance of survival.
On August 27, 1942, JD received his first dose of chemotherapy recorded as 0.1 mg/kg of synthetic lymphocidal chemical (the first chemotherapy treatment in the United States and in the world). Toxicology studies performed in rabbits had suggested such dosage. He received 10 daily intravenous injections, with symptomatic improvement noted after the fifth treatment. Biopsy following completion of the treatment course remarkably revealed no tumor tissue, and he could eat and move his head without difficulty. However, by the following week, his count of white blood cells and platelets began to decrease. The result was gingival (gum tissue) bleeding requiring blood transfusions. A week later, he was noted to have considerable sputum (mucus from the lung) production with recurrence of petechiae (red, purple and brown spots caused by bleeding from broken capillary blood vessels), necessitating an additional transfusion. By day 49, recurrence of his tumors has led to the decision of resuming chemotherapy. He died shortly afterwards.
Since early 1940s, the paradigm has not changed. The cancer cell has to be killed either by surgery, radiation therapy, chemotherapy and more recently immunotherapy. Hundreds of billions of dollars have been invested. Millions of molecules have been screened for their ability to kill cancer cells. Tens of thousands tested in mice, thousands in human beings. Cancer has become the focus of research that cannot find a cure for it. And the scientific research bubbles followed one another. Hope, hype and failures. Yesterday personalized chemotherapy, today immunotherapy or precision medicine. Just because a treatment is expensive and shrouded in hard-to-grasp science doesn't mean it works. Immunotherapy has been suggested in the treatment of an aggressive skin cancer, melanoma. Despite everyone's best efforts, mortality from melanoma continues to increase.
The most effective drugs used today date back from the 1960s and 70s. Fluorouracil, a cornerstone of the treatment of colon and rectal cancer has been patented in 1956. Doxorubycin used every day for the treatment of breast cancer has been approved in 1974. Cisplatin is a treatment for lung and colon cancer that has been licensed in 1978.
JD's history is thus interesting because it is very recent. Like the derivative from the gas of World War I, our cytotoxic chemotherapy drugs have major side effects. They kill white blood cells and platelets. The patients experience nausea and vomiting. They loose hair.
This apparent success at Yale turned out into a disaster. It froze research. Cancer was to be killed; there was no other option. As of today, chemotherapy can cure only a few pediatric cancers, Hodgkin's disease and leukemia. It is of no avail that despite tremendous efforts, eighty years later, nearly every patient with metastatic cancer relapses and dies.
Over the western world, for each death, the physician files a certificate and writes down the cause of death. Statistics can be drawn, comparing the evolution of the rate of cancer deaths over the years and the countries. The International Agency on Cancer Research (IARC) based in Lyon (France) is in charge of filing such statistical data, which can be seen at https://gco.iarc.fr/. The mathematicians consider the increase in the population and its aging. Overall, the rate of cancer deaths per 100.000 men or women of a given age has changed little over the past 60 years. In other words, there is no evidence that the war of cancer has been won. A few examples:
- Despite all the campaigns against sun tanning or in favor or early detection or even the most expensive immunotherapies, the death from melanoma (a deadly form of skin cancer) has been steadily increasing, whatever the country and the age bracket.
- The death rate of prostate cancer has remained stable despite the multiple innovations (prostatectomy, radiation therapy and new hormonal treatments).
- The death rate of breast cancer has steadily increased in the 80s and 90s to slowly decrease since then. Today, the chance of dying of breast cancer at a given age is about the same as 60 years ago. There is no demonstrable impact of early screening or targeted chemotherapy.
- The death rate from gastric cancer has been declining since the 1940s. The very reason is unknown. It may be the better preservation of foods and the advent of the refrigerator. The food are less likely to be rotten and that is probably why they are less cancer-prone.
Forty years ago, there was no financial incentive in cancer. The market of chemotherapy was the same as the one for constipation.
www.clo2.nl: Money!!! Today, the pharmaceutical industry sees cancer as the last frontier. The other opportunities are closed. The revenues of drugs targeting ulcer, cholesterol and high blood pressure appear limited and mature. Research has failed to open the treatment of neurodegenerative diseases. As a result, the revenues of eight of the ten most profitable drugs stem either for cancer or for the closely related autoimmune diseases.
The only hope for increased profit is cancer, where a lot of progress may be made in future. During the past few decades, the industry has lobbied for the increased use of chemotherapy. Forty years ago, palliative care was the treatment for most advanced cancers. The physician tried to hide the truth to the patient as long as possible. To conceal the word «cancer», words such as «oncology» and «neoplasm» have been coined.
Today, you have to warn the patient of his incoming death by providing every detail on his upcoming suffering. In our opinion, we prefer the humanity of the forgotten times of the past. Today, the vast majority of the patients take «benefit» from a few courses of chemotherapy before dying either of the progression of the tumor or of the side effects of the treatment. Instead of spending their limited time with their loved ones, the patients navigate between medical appointments and CT scans.
Not every cancer patient dies of this disease. But the ones, who survive, do not have the most aggressive form of cancer. The proportion of survivors from breast cancer patient has skyrocketed. The survival rate from early breast cancer is over 90% at five years. But behind closed doors, the debate rages. Is it worth treating these patients? Do they really have cancer? Meanwhile, the most aggressive form of breast cancers is as frequent and as deadly.
The medical community still debates about the utility of screening mammographies. On the one hand, the patients are grateful for their «cure», the industry sees an expanding market and the physician are grateful to help the patients. The physicians also enjoy the financial rewards from prescribing endless chemotherapy and radiation therapy sessions. On the other hand, the randomized trials have failed to demonstrate that screening mammographies improve breast cancer or overall survival rate of the patient, despite a number of needless surgeries and chemotherapies.
Welch, H. G. (2006). Should I be tested for cancer? Maybe not and here’s why. Univ of California Press.
It is written in the textbooks that breast cancer takes years to develop. The earlier you catch it, the better the prognosis. That view may not be correct and it is probable that the aggressive cancers develop within weeks or months not years. Yearly palpation of the breast and mammography detects more and more cancers. The vast majority of them are not aggressive. But screenings fail to detect the most aggressive cancers. In the group of women screened by mammography, compared to the control group, there is no difference in the number of lymph node metastasis during surgery or in the rate of disfiguring mastectomies for aggressive cancer. Hence, the number of deaths remain unchanged in the women screened for breast cancer.
Basic research followed the same path of clinical research. Cancer cells are malignant and deserve death. The cancer cells that refuse to commit suicide (apoptosis) for the greater good of the patient must be eliminated.
In the 1950s, the emergence and development of computers coincided with the discovery of DNA and genetic heritage. This led to a great temptation among biologists to reduce living things to a genetic code, which would provide explanations for all biological phenomena, including diseases.
Indeed, the color of peas, like that of eyes, is encoded by specific genes. Certain diseases do indeed originate from an anomaly in the genetic heritage. But the mistake was to extend these results to all diseases, especially those caused by aging. Today, there is a consensus that few cancers have a strictly genetic explanation. If a hereditary abnormality can explain the occurrence of certain cancers in children or young adults, the genetic factor does not explain the most frequent cancers that surface in mature or old people. The genetic trail therefore turned out to be erroneous. The genome is only one piece of the puzzle that we must unravel.
The discovery of the double helix of DNA and the advent of the computer sealed the fate of basic research. The DNA is a program, like the one in a computer. This means that the fate of the cell and the human body is entirely under control of the DNA. Molecular biology became the key tool in modern biology erasing other older approaches, resulting in gradual closure of physiology laboratories. Nowadays, experiments on rodents are banned, under the pretext of animal welfare. The cells isolated and well fed in Petri dishes became the only tool of the researchers. These cells could be used for exploration. Details of their genome and their proteins were the subject of endless publications. But we are very far from the cancer patient who dies of its metastases.
To look more closely, the assumption of key role of genes, reminds us the belief in predestination. Those who adhere to it, believe that God writes their destiny in The Big Book even before their birth. They are convinced to have no other choice, but to follow it and to undergo it. It would be the same if there were the intelligence gene or even the crime gene. “Excuse me !”, would say their carriers, “It's not my fault, it's my genes !”
Every event of life can be explained by the sacred code of life. There are hundreds of publications explaining that homosexuality should be written somewhere in the DNA. This is a heated debate. Some agree with this hypothesis, others don’t.
For many scientists, DNA necessarily encodes Alzheimer, cancer and intelligence. There is some limited truth to this hypothesis. Genetics is responsible for only 3% of all breast cancers. This means that most of these cancers are not hereditary. The cancers among young adults run into families and can be explained by the transmission of an abnormal gene, an oncogene. The word «oncogene» was framed in the 1970s to name these genes which can cause cancer. Today there are no universal cancer genes, but a hundred of different oncogenes each playing a role in some rare form of hereditary cancers such as leukemia.
The most common type of breast and colon cancer is not hereditary. The genome of the patient is completely normal. To the opposite of the normal cells, the cancer cells have an abnormal genome. There are hundreds of thousands of mutations in the genome of the cancer cell. There is no universal pattern of genetic abnormalities. The mutations are different from one cancer cell to the next. The very reason for the abundance of mutations is unknown.
This gene-centered paradigm has led to disasters. Today, every new chemical entity has to be screened for its cancer posing risk. To screen for carcinogenicity of a chemical compounds, the scientist check if the molecule can target the DNA. It is deemed carcinogenic, if such damage can be demonstrated. Multiple extracts of the carrot or the potato target the DNA and cause mutations, but most pesticides target the mitochondria, an organelle of the cell not the DNA. These pesticidesy probably cause cancer, but not mutations.
The general practitioner had good knowledge of the toxicity of tobacco smoke, decades before it was demonstrated in laboratories. In fact, it was because the mice did not develop lung cancer that the tobacco industry could claim its harmlessness. The rodents breathe only through the nose. They develop nose cancer, not lung cancer.
It is always very difficult to see the naked truth. The way we perceive cancer needs to change. Cancer is not the fight of evil against the good. Chemotherapy does not cure most common cancers. Mutations do not cause most cancer. There are neither good cells nor bad cells. There are no crazy cells. They do not commit suicide. Laws of physics are responsible for the apparition of cells, and they are doomed to obey such laws.