Origins of Disease & Cancer Overview

• Lecture 4 discusses the origins of human diseases and provides an overview of cancer.
• By the end of the lecture, students should be able to discuss the history of disease, recall systems theory of life, classify diseases, and describe cancer origins, types, and treatments.

History and Theories of Disease Origin

• Medicine was long dominated by certain disease theories, until Rudolf Virchow declared in the 19th century that diseases are manifestations of life processes under altered conditions, not independent entities.
• "Disease" is defined as an impairment of the normal state of an organism that interrupts or modifies normal functions, or anything that causes the body to stop working properly.

Systems Theory of Life

• Living organisms are systems in dynamic equilibrium internally, not just with the external environment.
• Survival requires continuous exchange of energy and matter with the external environment, while maintaining a stable internal environment.
• Homeostatic mechanisms help organisms adjust to internal environment changes through behavioral responses, immune reactions, and detoxification.
• Disease occurs when internal environmental changes exceed the organism's adjustment capacity or when adjustment mechanisms fail.
• Homeostasis involves maintaining steady internal physical/chemical conditions for optimal function within certain preset limits.

Disease Examples and Classification

• Diseases can be triggered by an "unbalancing change" in the internal environment, such as infections where the immune system fails, or cancer where cell growth is uncontrolled due to genetic abnormalities and defense mechanism failure.

Congenital Diseases

• Arise from hereditary DNA abnormalities, causing impairments in growth and development, or from various issues during pregnancy/childbirth, interfering with normal fetal/perinatal health.
• Examples include Down's syndrome and congenital rubella.

Acquired Diseases

• Result from pathological onsets like infections, allergic reactions, nutrient deficiencies, mechanical wear, chemical ingestion, or trauma.
• Examples include tuberculosis, asthma, anemia, and fractures.

Evolutionary Perspective

• Human organisms experience unfavorable exchanges with the external environment because dependence is mandatory, and the external environment is fundamentally hostile.
• Living organisms operate as open, non-equilibrium thermodynamic systems, exchanging energy/matter to reduce internal entropy.
• Energy and matter extraction from the environment can cause illness because the same elements in abiotic, biotic, and human environments can be harmful. Example: Sunlight leading to cancer.

McKeown's Disease Classification

• Classification attempts to categorize all diseases into three groups.
• Prenatal diseases manifest before birth.
• Diseases of poverty are linked to deficiencies/hazards from lacking life's essentials.
• Diseases of affluence stem from maladaptation/hazards related to industrialization.

Disease Types

• Infectious diseases spread and are caused by pathogens like bacteria and viruses; contagious diseases spread easily through contact.
• Non-infectious diseases do not spread and arise from environmental or abiotic factors; chronic diseases are long-term illnesses with slow progression.
• Genetic diseases are inherited or spontaneous, caused by abnormal genes or chromosomal issues.

History of Cancer

• Cancer has existed as long as animals have; evidence is found in dinosaur bones and mummies.
• Operations to remove cancer were documented in ancient Egypt.
• Cancer was less common due to shorter lifespans from infectious diseases.
• Hippocrates named it "cancer" (crab) in Greek.
• The origin of cancers remained debatable until the mid-1970s.

Theories of Cancer Origin

Carcinogen Theory

• Cancer-causing agents like certain chemicals, coal tar emissions, radiation, tobacco smoke, and asbestos.

Virus Theory

• Viruses were originally thought as the main cause.

• Rous's experiments with chicken tumors showed the transfer of cancer via tumor extract.

• Abelson's discovery showed leukemia viruses could mutate to cause bone marrow cancer in mice.

• Both the carcinogen and virus theories fell short in explaining most human cancers since many have no viral connections.

• Cancer research now points to cancer ultimately being a disease caused by genetics.

• Bruce Ames proposed the Ames test to predict the ability of chemicals to cause mutations in DNA

• Carcinogens (like X-rays) damage DNA, causing mutations in genes, contributing to cancer.

• Cancer can be triggered by oncogenes or the genes that causes normal cells to form tumors.

Types of Cancer

• There are over 110 types of cancer, which can be divided in five categories depending on the tissue involved.
• Carcinoma being the most common ( originating in epithelial tissue)
• The other main categories are lymphoma, leukemia, sarcoma, and melanoma.

Cancer Therapy

• Therapies are mechanical, physical, chemical, and biological.

Mechanical Treatment

• Surgery is the most frequently used treatment option.
• Surgery is a localized treatment recommended for patients who can tolerate surgical procedures and anesthesia.
• Surgical anesthesia was introduced in 1846.

Physical/Chemical Treatments

• Physical: radiation, light, heat or include radiation therapy (called radiotherapy), photodynamic therapy, and hyperthermia.
• Chemical: chemo-therapeutic and targeted drugs
• Radiation can cause and cure cancer.
• X-rays were discovered in 1895 by Wilhelm Röentgen.
• Radiation therapy uses ionizing radiation to kill cells and is used in about 50% of localized tumors.
• Hyperthermia is a modest rise of temperature, in the range of 39 to 48 Celsius degrees, to kill the cancer cells.

Chemical Treatment

• Chemotherapy, using chemicals to treat diseases.
• Action of nitrogen mustard based war gas.
• Many agents used have significant toxicities
• All current chemotherapeutic drugs can be classified according to their mechanism of action.

Biological Treatment of Cancer

• Therapies involve antibodies, proteins, viruses, and cells;
• Immunotherapy stimulates the immune system to respond to the tumor; tumor antigens are substances produced by tumor cells that initiate an immune response.
• Oncolytic viruses are those that preferentially infect and destroy cancer cells; they exploit vulnerabilities that cancer cells exhibit compared to normal cells.

Keywords

• Disease: An impairment of normal function.
• Living organisms: Open, non-equilibrium thermodynamic systems exchanging energy/matter.
• Homeostasis: Stable internal physical/chemical conditions.
• Prenatal Diseases: Manifested before birth.
• Diseases of Poverty: Linked to lack of life's essentials after birth.
• Diseases of Affluence: Related to maladaptation/industrial hazards after birth.
• Infectious Diseases: Spread by bacteria, viruses, fungi, etc.
• Non-infectious Disease: Caused by environmental/abiotic factors, not spread.
• Carcinogen = Mutagen Theory: Says in essence, carcinogens such as X-rays and chemicals act by damaging DNA, thereby creating mutations in genes of targeted cells;
• Virus Theory: Proposed that viruses alone cause cancer.
• Cancer: A disease of genes
• Cancerogenesis: the process in which health (normal) cells are transformed into cancer (tumor) cells.
• Chemotherapy: Describes the use of chemicals to treat diseases.
• Immunotherapy is the treatment of diseases by stimulating or suppressing an immune response.
• Oncology: The study of tumors.
• And more defined terms.