The History of Cancer and Its Treatments

Russell Doolittle, PhD

Osher Lecture 1 April 10, 2013

Some Sources Used in Preparing for This Course

John Cairns. Cancer, Society and Society. W.H. Freeman, 1978.

John Cairns. Matters of Life and Death. Princeton Univ. Press, 1997.

Siddhartha Mukherjee. The Emperor of All Maladies. Scribner, 2010.

L. Tomatis (editor). Cancer: Causes, Occurrence and Control. IARC, 1990.

As well as various textbooks, New Yorker articles, and lots of Googling.

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)

More Historical Moments

Andreas Vesalius (1514-1564) great anatomist and illustrator

Surgical removal of solid tumors becomes common after introduction of ether as an anesthetic (1842)

Radiation used against tumors, only five years after discovery of X-rays (1895)

Rudolf Virchow (1827-1902) “omnia cellula e cellula

Invention of the microscope (Van Leeuwenhoek, 1676)

Schleiden and Schwann (1838) cell theory

Introduction of antisepsis by Joseph Lister makes surgeryIn general much safer (1865)

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.

Lip

Tongue and mouth

Salivary glands

Nasopharynyx

Oesophagus

Oropharynyx-hypopharynx

Stomach

Colon

Rectom

Liver

Pancreas

Larynx

Lung

Bone

Mesothelioma

Soft tissue sarcoma

Melanoma

Other skin cancers

Breast

Uterine-cervix

Choriocarcinoma

Corpus uteri

Prostate

Ovary

Testis

Penis

Bladder

Kidney

Eye

Nervous system

Thyroid

Non-Hodgkin lymphoma

Hodgkin’s disease

Multiple myeloma

Leukemia

Cancers are also defined by the type of cell in which they originate.

Carcinomas (epithelial cells, sheets, etc.)

Sarcomas (supporting tissues, including bone and muscle)

Leukemias and lymphomas (circulating white blood cells)

(more than 90% of cancers)

Cancer is a cellular disease:

Cancer is a molecular disease:

Cancer is a genetic disease:

(cell biology: mitosis, meiosis, cell cycle, etc.)

(structure of DNA, RNA, proteins, etc.)

(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.

The Biology of Cancer

Surgery

Radiation

Chemotherapy

Immunotherapy

The Common Treatments

Other Biotherapy (marrow transplants, etc)

Some people ascribe to alternative approaches.

A view from alternative medicine.

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.

Some Apparent Paradoxes

Prevention is the ideal strategy.

Avoid environmental insult if possible.

Early associations about cancer and the environment

1775: (Percival Pott) Chimney sweeps develop scrotal cancers

1850: The industrial revolution contributed greatly.

1890: bladder cancer, workers in dye factories.

1853-1860: The first cigarette factories.

1762: (Hill) Snuff is carcinogenic.

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).

An unexpected association between cancer and diet.

Cancer is age-related.

Some leukemias are most common in children.

But the incidence of most cancers increases with age.

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.

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).

diphtheria

If we are to understand these associations between cancerand age and diet and the environment, etc., we will haveto re-acquaint ourselves with some fundamental biology and chemistry.

Speaking generally, the more cell divisions that occur in any tissue or organ, the higher the likelihood that mistakeswill occur that lead to uncontrolled cell divisions.

What unifies all the different kinds of cancer is that theyare all the results of mistakes that are made in copyingDNA just before any cell divides.

DNA: A Double-Helix

phosphate

Complementary nitrogen bases(A:T, G:C) directed inward

One base pair

Sugars(desoxyribose)

A:TG:C

links

Next time we will begin with the rationale behindsome 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.