The History of Cancer and Its Treatments

1. The History of Cancer and Its Treatments Osher Lecture 1 April 10, 2013 Russell Doolittle, PhD

2. Some Sources Used in Preparing for This Course Siddhartha Mukherjee. The Emperor of All Maladies. Scribner, 2010. John Cairns. Cancer, Society and Society. W.H. Freeman, 1978. John Cairns. Matters of Life and Death. Princeton Univ. Press, 1997. L. Tomatis (editor). Cancer: Causes, Occurrence and Control. IARC, 1990. As well as various textbooks, New Yorker articles, and lots of Googling.

3. Some Historical Moments Inhoptep (an Egyptian physician, as translated from a 2625 BCE papyrus) Herodotus (Greek historian, ca 450 BCE, telling the story of Atossa, queen of Persia) Hippocrates (Greek physician, ca 450 BCE, lamenting there is no cure) Celsus (Aulus Cornelius) (Greco-Roman historian of medicine, 2nd century CE) Galen (190 CE) Expert Roman anatomist and illustrator. Paul of Aegina (7th century, CE). Well traveled Greek physician. Wild notion that cancer might be contagious (17th century, CE)

4. More Historical Moments Andreas Vesalius (1514-1564) great anatomist and illustrator Invention of the microscope (Van Leeuwenhoek, 1676) Schleiden and Schwann (1838) cell theory Rudolf Virchow (1827-1902) “omnia cellula e cellula Surgical removal of solid tumors becomes common after introduction of ether as an anesthetic (1842) Introduction of antisepsis by Joseph Lister makes surgery In general much safer (1865) Radiation used against tumors, only five years after discovery of X-rays (1895)

5. Breast Kidney Lip Liver Pancreas Tongue and mouth Eye Uterine-cervix Choriocarcinoma Salivary glands Larynx Nervous system Corpus uteri Thyroid Nasopharynyx Lung Hodgkin’s disease Mesothelioma Oropharynyx-hypopharynx Ovary Oesophagus Bone Non-Hodgkin lymphoma Prostate Testis Multiple myeloma Soft tissue sarcoma Stomach Leukemia Melanoma Colon Penis Rectom Bladder Other skin cancers There are more than 200 defined types of human cancer. Many of these are quite rare. About three dozen cancers are commonly described by site of origin.

6. Cancers are also defined by the type of cell in which they originate. Carcinomas (epithelial cells, sheets, etc.) (more than 90% of cancers) Sarcomas (supporting tissues, including bone and muscle) Leukemias and lymphomas (circulating white blood cells)

7. The Biology of Cancer Cancer is a cellular disease: (cell biology: mitosis, meiosis, cell cycle, etc.) (structure of DNA, RNA, proteins, etc.) Cancer is a molecular disease: Cancer is a genetic disease: (mutations, deletions, duplications, etc.) Cancer is a developmental disease: (cell fates, stem cells, cell death, etc.) We will also need to discuss epidemiology (statistics), ionizing radiation (physics), and much else.

8. The Common Treatments Surgery Radiation Chemotherapy Immunotherapy Other Biotherapy (marrow transplants, etc) Some people ascribe to alternative approaches.

9. A view from alternative medicine.

10. Some Apparent Paradoxes mutagen (an agent causing mutations in DNA) carcinogen (an agent causing cancer) There is a strong correlation between mutagens and carcinogens. Some agents used in chemotherapy are also mutagens Similarly, radiation, which is used as a treatment for cancer, is well known to cause mutations and to lead to cancer.

11. Prevention is the ideal strategy. Avoid environmental insult if possible.

12. Early associations about cancer and the environment 1762: (Hill) Snuff is carcinogenic. 1775: (Percival Pott) Chimney sweeps develop scrotal cancers 1850: The industrial revolution contributed greatly. 1853-1860: The first cigarette factories. 1890: bladder cancer, workers in dye factories.

14. Another early association of cancer and lifestyle. 1713: Ramazzini. Nuns at increased risk for breast cancer ( Confirmed by Rigoni-Stern in 1842) Attributed (correctly) to the lack of an active reproductive life (no pregancy, lactation).

16. An unexpected association between cancer and diet.

18. Cancer is age-related. Some leukemias are most common in children. But the incidence of most cancers increases with age.

20. Human life-spans in general began increasing in the mid-19th century. We have been winning the war against infectious disease. But as a consequence the chances of contracting a cancer have increased.

24. The most recent weapons in this war have been antibiotics. But before those came vaccination (Jenner, cowpox, 1796) and simple public health measures (e.g., John Snow, 1854). Clean water, better plumbing, reasonable laws. TB was greatly reduced in cities by laws against spitting (New York, 1896).

27. diphtheria

29. If we are to understand these associations between cancer and age and diet and the environment, etc., we will have to re-acquaint ourselves with some fundamental biology and chemistry. What unifies all the different kinds of cancer is that they are all the results of mistakes that are made in copying DNA just before any cell divides. Speaking generally, the more cell divisions that occur in any tissue or organ, the higher the likelihood that mistakes will occur that lead to uncontrolled cell divisions.

30. Sugars (desoxyribose) phosphate links One base pair A:T G:C Complementary nitrogen bases (A:T, G:C) directed inward DNA: A Double-Helix

31. Next time we will begin with the rationale behind some chemotherapeutic agents (e.g., aminopterin). Don’t be put off by the chemical structures. We’re mainly interested in the notion of design rather than the details.