Discovery of Normal Cell Biology

DISCOVERY OF NORMAL CELL BIOLOGY SLIDE 1. TITLE. Cancer is always topical in the 21st century-particularly in the demographic that takes Senior College courses. There is fascinating science and fierce human drama associated with the disease. SLIDE 2. OUTLINE OF THE COURSE We will lecture on six topics in this course. Today we lecture on normal cell biology and cancer biology, so you can better understand the how and why of cancer’s effects on patients. The first lecture may be the most challenging as it reviews basic science. In the 2nd lecture we discuss the causes of cancer, prevention of cancer, and screening tests for cancer. In the 3rd lecture we will discuss the evaluation of the cancer patient. In the 4th lecture we will discuss the treatment of cancer. In the 5th lecture we present seven cases that illustrate how the knowledge gleaned in the first four lectures was employed to help actual patients. In the sixth and final lecture we will discuss what is required of the patient; oncologist and care team; and the health care system to best help cancer patients. I hope to be permitted some philosophical reflections on patient care reflecting almost half a century of clinical training and practice. A heavy dose of medical history will be supplied in each lecture because medical history is interesting and will help you understand how it is we came to do what we do. SLIDE 3. DILBERT STRIP ON ZOOM TECHNOLOGY I’m not a fan of this new-fangled ZOOM technology and worry it will poleax me any minute. I will soldier on with information technology support. SLIDE 4. DILBERT WITH A COMPLICATED PRESENTATION The lectures are pitched to the intelligent layman. We’ve all felt like Alice after listening to Dilbert’s lecture. The lingua franca of oncology can be hard to follow. I’ll try my best to define the terms and simplify the concepts. I’ll periodically take any questions you relay to Dr. Scott both during the lectures, and at the end of the lectures. We can provide transcripts of the lectures if you so desire. If I were you I’d relax, listen to the lecture and view the slides. I’d raise any questions I had at the time I thought of it. I’d get the transcripts of the lectures and review the transcripts after the lectures. SLIDE 5. BURDEN OF CANCER IN THE USA. I would hazard the guess everyone auditing this course has had someone near and dear who has had to cope with cancer. The statistics are sobering. One out of 225 American were diagnosed with cancer in 2020. 1 out of 630 Americans died of cancer in 2020-1 out of every 530 men and 1 out of every 740 women. African-American men were the most affected demographic: 1 out of 439 died of cancer.. Asian-American women were relatively least afflicted: 1 out of 1, 1168. There are 17 million cancer survivors in the USA. 40% of Americans will receive a cancer diagnosis in their lifetime. SLIDE 6. DEFINITION OF CANCER. We lecture today on normal cell biology. In order to appreciate what causes cancer, it is important to understand normal cell biology. With this understanding we then lecture on cancer biology. Cancer is basically altered cells caused by mutations in the genome. SLIDE 7. SCHOOL OF ATHENS The Greeks, as was their wont, got the ball rolling on characteriZing normal cell biology with speculative natural philosophy. Pythagoras hypothesiZed, around 530 BC, that “likeness” was carried in the male semen, after coursing through a man’s body and absorbing vapors from each part. Aeschylus’s Eumenides was performed in 458 BC. In the play Orestes was on trial for matricide. Apollo, called to judge, reasoned a father’s sperm carries “likeness”, while the mother just drips nutrients through the umbilical cord into the child. Apollo judged Orestes innocent since he was avenging a more serious crime-his father’s murder. Aristotle dismantled the Pythagorean theory of spermism by noting children also inherit features from their mother and other ancestors. He noted “In Sicily a woman committed adultery with an Ethiopian; the daughter did not become an Ethiopian, but the granddaughter did.” SLIDE 8. GREGOR MENDEL Father Gregor Mendel, was an Augustinian monk at St. Thomas’s Abbey in Brno, Moravia. Father Mendel distilled a decades worth of scientific work breeding peas into a paper published in the 1866 Proceedings of the Brno Natural Science Society. Father Mendel had documented the laws of inheritance. Father Mendel was well aware of the relevance of his research to Darwin’s theory of natural selection. But Father Mendel’s attempts to interest professional scientists in his work failed. Father Mendel’s epochal research languished in obscurity for 40 years. In 1905 William Bateson, “Mendel’s bulldog”, finally recognized the importance of Father Mendel’s research. Bateson publicized Mendel’s conclusions. Bateson also coined the word genetics from the Greek word “genno”-to give birth. In 1909 the word gene was first used for Mendel’s unit of heredity. The sum total of all our genes is the genome. SLIDE 9. ALLELES Alleles are one of two or more alternative forms of a gene that are found at the same place on a chromosome. Another way to remember what alleles are is to think of them as allies: the gene on the chromosome from the father and the gene on the “homologue” chromosome of the mother ally to assign characteristics to the baby. The male and female alleles combine to assign hair color, eye color, etc. On the slide capital A is the dominant gene, coding for yellow peas. Small a is the recessive gene coding for green peas. In the Punnett square the peas are yellow when there are two dominant Capital A genes paired, yellow when a dominant capital A and recessive small a are paired, and only green when two recessive “green genes” are paired. 75% of the peas are yellow and 25% green over time. However, what happens to any individual pea is akin to a roll of the dice. SLIDE 10. CHROMOSOMES ARE THE CELLULAR BASIS OF HEREDITY In the 1890’s Theodore Boveri, a German embryologist working with sea urchins in Naples, proposed that genes resided in chromosomes, which resided in the nucleus of cells. Walter Sutton, a farm boy from Russell, KS who attended the University of Kansas, was later a graduate student at Columbia. Sutton’s research at Columbia with grasshopper sperm and egg cells confirmed Boveri’s findings that genes resided in chromosomes in the nucleus of cells. In 1905 Nettie Stevens of Bryn Mawr College documented “maleness” in worms was determined by the Y chromosome. Thomas Morgan then documented genes for certain characteristics were physically linked on the chromosomes of fruit flies in 1912. SLIDE 11. CHROMOSOME PAIRS As pictured in the slide, we have 23 pairs of genes in the nucleus of each cell in our body. In each chromosome one of the strands comes from the father and one comes from the mother. The father’s strand is paired with its counterpart, called a homologue, from the mother. The two homologues are joined at the center by a centromere. In the lower right corner of the slide the sex chromosomes are pictured. Women inherit two X sex chromosomes. Men inherit an X and Y sex chromosome. Note how small the Y chromosome is. The genes on the Y chromosome instruct the embryo to turn into a male at age 6-7 weeks. Instructing the embryo to turn into a male is the only job a Y chromosome is asked to do. One of the X chromosomes also becomes inactive after conception. The inactivated X chromosome turns into something called a Barr body. The inactivated X chromosome (Barr body) is inactivated by a process called epigenetics which we will soon discuss. After the chromosomes were proven to be the locus of genes and heredity the search was then on for the molecular structure of chromosomes. The molecular structure of chromosomes needed to be characterized before we could fully understand the mechanisms of heredity and cancer. SLIDE 12. STRUCTURE OF THE HUMAN CELL As early as 1869 a Swiss biochemist, Friedrich Miescher, documented the dense, swirling strands of chemicals he found in salmon sperm and human white blood cells were acidic and located in the nucleus of those cells. By the early 1920’s biochemists documented nucleic acid came in two forms: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). The cytoplasm is the area in the cell outside the nucleus. It is important to remember the mitochondrion has its own separate DNA. The mitochondrion is where respiration takes place and energy is produced. The ribosomes are sites where proteins are manufactured through assembly of amino acids. In 1944 Oswald Avery documented DNA was the carrier of genetic information. Maurice Wilkins and Rosalind Franklin produced clear X-ray crystallography images of DNA at King’s College London in 1952. SLIDE 13. WATSON AND CRICK WITH THE DOUBLE HELIX On February 28, 1953, Francis Crick and an American graduate student James Watson deduced the double helical structure of DNA at Cambridge University. They deduced the double helical structure of DNA by building on the experimental data collected by Wilkins and Franklin and tinkering with the toy model pictured in the slide. Watson and Crick won the competition to determine the structure of DNA, lasting fame and the 1962 Nobel PriZe in Medicine for their discovery. SLIDE 14. DOUBLE HELIX STRUCTURE OF DNA Pictured is a DNA molecule, shaped in the double helix.

Load more