4-23-10 disease-color

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Unformatted text preview: People Helping People Clicker Question Type 1 diabetes occurs when the pancreatic endocrine cells that secrete insulin become the targets of _____________. SI A) macrophages B) B cells C) cytotoxic T cells D) helper T cells E) digestive enzymes from the pancreatic exocrine cells Where are we? Last Last time I talked about… – how our body protects us from germs – the innate immune system – the acquired immune system that learns, remembers remembers and recognizes self from non-self. non– autoimmune diseases result when the immune system cannot distinguish between self and nonnon-self This This time I will talk about… – diseases and their prevention, treatment or cure – testing and diagnosis Free Free Coffee this Wednesday! Hippocrates: Hippocrates: Father of Medicine Diseases have natural causes and can be treated rationall rationally. Poor diet diet, terrible weather weather and bad water water are the major causes of disease. Hippocratic Oath 1 DisDis-Ease or Disease According to Hermann Boerhaave (1724), the aim of medicine is to give ease to suffering give ease to suffering (i.e. dis(i.e. dis-ease) and a cure involves changing the disease into health. Diseases, Disorders or Conditions we have Discussed this Semester Scurvy, Scurvy, Beriberi, Pellagra, Rickets Phenylketonuria, Phenylketonuria, Alkaptonuria (black urine disease) Ulcers Ulcers Lou Lou Gehrig’s disease Severe Severe combined immunodeficiency (SCID) AIDS and opportunistic infections AIDS and opportunistic infections Hemophilia, Hemophilia, Sickle cell anemia, Thalessemia Type Type 1 and Type 2 diabetes Muscular Muscular dystrophy Intersexuality Intersexuality Multiple Multiple sclerosis, Dwarfism, Lupus, Lymphoma, Leukemia Schizophrenia, Schizophrenia, Parkinson’s disease, Depression Pneumonia, Pneumonia, Tuberculosis, Small pox, Cholera, Anthrax, Rabies, Polio Heart Heart disease, Pulmonary embolism, Stroke Factors that Influence Health and Disease Environmental Environmental Factors – Sanitation and microbes (prions, which are self(prions, selfreplicating proteins, viruses, bacteria, fungi, protozoa) – Toxins and hormones (cigarette smoke and estrogens) – Nutrition (vitamins) (vitamins) – Stress (at school, home and work) and other psychosomatic factors – Wounds (head wounds can lead to epilepsy) Many Scientific and Medical Heroes Have Fought Quixotically Against the Scientific Establishment for Your Health and WellWellBeing Genetic Genetic Factors – Inborn errors in metabolism (sickle cell anemia, thalessemia, alkaptonuria, phenylketonuria) thalessemia, alkaptonuria, phenylketonuria) Environmental Environmental and Genetic Factors Interact T. S. Kuhn: Science Progresses through Science Scientific Revolutions—that is by Overturning that Revolutions— which was Previously Believed Believed Henry H. Bauer: The Dominant Group Resists New Ideas 2 C. H. Waddington: Be Aware of Cow Dung Co Conventional Wisdom of of the the Dominant Group Thatige Skepsis “An Active Skepticism is that which unceasingly that which unceasingly strives strives to overcome itself and by well directed Research to attain to a kind of Conditional Certainty.” Thomas H. Huxley Skepticism Profiles in Courage: Edward Jenner With With the help of Sarah Nelmes and James Phipps, Edward Jenner invented an effective vaccine against the deadly smallpox. When When Jenner reported his results to the Royal Society; results to the Royal Society; they they suggested that he should not risk his reputation by presenting something "so "so much at variance with established knowledge". Jenner Jenner published his work privately and vaccinations for smallpox became common practice. The greatest value The greatest value of of science is the freedom to doubt! Richard Feynman The The Scientific Establishment did not Believe Louis Pasteur The The idea that germs could make an animal healthier seemed unbelievable to the editor of The Veterinary dit Th Press, who challenged Pasteur to a public test. Pasteur Pasteur showed that his vaccine protected the sheep from anthrax and won the admiration of the public. The Medical Establishment Pooh-Poohed Poohthe Future Nobel Laureate Ilya Mechnikov Working Working with little or no pay, Elie Mechnikov concluded that pus was due to a natural defense mechanism and consisted of phagocytes that would eat the bacteria that eat the bacteria that caused caused the infections. It It took years before the medical establishment could conceive of the white blood white cells in pus having a curative function and that they were not the carriers of infection to the rest of the body. 3 Joseph Goldberger Was Ridiculed Joseph Goldberger, his wife and friends held “filth parties” to demonstrate to an demonstrate to an incredulous incredulous scientific community that pellagra is not a contagious disease, but due to a vitamin B3 (niacin) deficiency. Barry Marshall Was Heroic At At a time when the scientific community believed that all ulcers were caused by stress or spicy food, Barry Marshall decided to prove that ulcers could also be caused by a bacterial infection. He He drank a culture of Helicobacter Helicobacter and and suffered a severe inflammation of the stomach. His research showed that Helicobacter Helicobacter was the major cause of ulcers. Autopsy— Autopsy—To See for Oneself During During the Renaissance, physicians and artists performed autopsies in order to probe Nature’s secrets and see the anatomy of the body for for themselves. During During the Enlightenment, Giovanni Battista Morgagni (1761) performed autopsies to investigate the changes in changes anatomy correlated with different diseases. National Geographic Interactive Autopsy Robert Carswell (1838) Illustrator Robert Carswell. Pathological Anatomy. Illustrations of the Elementary Forms of Diseases. 4 Discoveries, By Definition, Are Always at Odds with Conventional Wisdom Forceps Were Invented to Help with Difficult Deliveries It It is ironic, as I will present to you now, that autopsies, which were introduced to understand the causes of disease led to causes autopsies autopsies that caused disease in the case of childbed fever. The The solution to the problem was at odds with conventional wisdom and required courage. courage Until the mid-17th century, women gave birth at home midbut the birth of babies in atypical positions were difficult and 2.5% of the mothers and babies died during childbirth. Lying-in hospitals were created where Lyingphysicians could safely deliver babies using forceps. forceps. Modern Vaginal Delivery of a Breech Baby Chamberlen Chamberlen Family (16th Century) The The forceps reduced the mortality rate for women and their fetuses by changing the position of the fetus in the uterus fetus in the uterus. Before Before the invention of forceps, difficult deliveries generally ended with an abortion of the baby, or the death of both mother and fetus. www.wondersandmarvels.com Forceps Used for Atypical Deliveries 18th Century www.thegarret.org.uk www.med.yale.edu 19th Century 20th Century 5 Epidemic of Puerperal Fever (Childbed Fever) With With the advent of lying-in hospitals lyingcame epidemics of the fatal epidemics of puerperal fever (childbed fever). The The conventional wisdom at the time indicated that puerperal fever was caused by a miasma (bad air) or by caused by miasma air or by the the woman’s state of mind (shame when touched by a physician who was male or hysteria caused by a disturbance in the uterus (hystera)) and was not contagious. However, However, the site in which the placenta used to be attached is a large open wound susceptible to infection. No No One Listened to Alexander Gordon Alexander Alexander Gordon (1795) used epidemiological epidemiological evidence to suggest that puerpural fever was transmitted from patient to patient by the midwives and physicians. He He wrote in his Treatise on the Epidemic of Treatise Puerperal Fever arrived at that certainty in the Puerperal Fever, "I arrived at that certainty in the matter matter that I could venture to foretell what women would be affected with the disease, upon hearing by what midwife they were to be delivered, or by what nurse they were to be attended, during their lyinglying-in: and almost in every instance my prediction was verified.” Gordon’s Gordon’s words were ignored by the medical establishment. Oliver Wendell Holmes In In America, Oliver Wendell Holmes (1843), father of Associate Justice Oliver Wendell Holmes Jr., wrote in The The Contagiousness Of Puerperal Fever that The disease known Fever that “The disease known as as Puerperal Fever is so far contagious as to be frequently carried from patient to patient by physicians and nurses.” His His evidence was that the frequency of the disease was correlated with who the doctor was more than any other factor. Doctors are gentlemen… The The key factor, according to Holmes, was whether or not a given doctor washed his hands routinely, for example, did the did doctor wash his hands after performing an performing an autopsy and and before before delivering a baby? Doctors Doctors were insulted by Holmes’ conclusion. Charles Delucena Meigs (→) gave Holmes a typical reply, "Doctors are gentlemen, and gentlemen's hands are clean." Where Was Conventional Women’s Medicine at the Time? Ignaz Semmelweis Semmelweis Semmelweis (1844) noted that when medical students delivered babies, 18% of all women giving birth died of puerperal fever while only 2% died when midwives or midwifery students performed the deliveries. Even Even stranger, puerperal fever was rare in women who gave birth before they arrived at the hospital. Semmelweis Semmelweis realized that medical students and doctors, but not the midwives, performed autopsies each autopsies morning on women who had died in the hospital the previous day, but he did not immediately appreciate the connection between the two observations. In the 19th and early 20th centuries, doctors cured hysteria manually and later electromechanically by inducing a “hysterical paroxysm” (orgasm). http://www.slate.com/id/2121835/slideshow/2121919/fs/0//entry/2121909/ Semmelweis Medical Museum 6 Cadavers vs. Phantoms Semmelweis Semmelweis also realized that the physicians were teaching the medical school students how to deliver babies using real human cadavers of mothers and babies who had recently died of puerperal di fever. fever. The The use of cadavers was a new advance in the medical education of obstetricians. Prior to using the cadavers cadavers, the students learned how to deliver babies on models of the human body known as phantoms. phantoms Johann Klein had an Alternative Hypothesis Ignaz Semmelweis’s boss, Johann Klein believed that more women died of puerperal fever when male doctors were delivering than when female midwives were when female midwives were delivering delivering because the male doctors offended the offended woman’s modesty which brought on hysteria. Semmelweis could not believe that this could explain why the prostitutes would die after a physician, who was male, delivered the baby. Ignaz Semmelweis Jakob Jakob Kolletschka (1847), a professor of forensic pathology died of septicemia (blood septicemia poisoning) after cutting his hand with a scalpel during an autopsy. On On reading the report of Kolletschka's autopsy, Semmelweis was struck by the similarity of the pathological findings to those similarity of the pathological findings to those of of women who had died of puerperal fever. He He wrote: "Suddenly a thought crossed "Suddenly my mind: childbed fever and the death of Professor Kolletschka were one and the same. His sepsis and childbed fever must originate from the same source . . . the fingers and hands of students and doctors, soiled by recent dissections, carry those death-dealing cadavers' deathpoisons into the genital organs of women in childbirth ....” Infectious Hospitals Hand Hygiene Problem Solved? Semmelweis Semmelweis began experimenting with various sanitizing agents and then ordered that all doctors and medical students wash their wash hands hands in a chlorinated chlorinated lime solution before delivering babies and performing vaginal exams. Instantly, the Instantly, the mortality rate from puerperal fever fell from 18% to less than 3%. 7 Ignaz Semmelweis: Genius or Loon? Semmelweis: The The doctors did not like having to wash their hands like little kids and Semmelweis was fired fired from his position. His findings were not accepted during his lifetime. In In 1865 he was committed to committed a mental institution because because he couldn’t take the way his research was either dismissed or ridiculed. He died of an infection from a cut on his finger two weeks later. Accident Accident or suicide??? That Mothers Might Live (1938) Semmelweis (2001) Historical Fiction about Semmelweis 8 A Real Opera “Soap Opera” http://www.raymondlustig.com/Doctors_Ward_Page.html http://www.raymondlustig.com/Doctors_Ward_Page.html Kurt Vonnegut “My “My hero is Ignaz Semmelweis.” “I “I will go on to recommend to those graduating from colleges everywhere in the colleges everywhere in the world world this spring that their hero be Ignaz Semmelweis.” If You Think Childbed Fever is a Disease of the Past, You Are Wrong. In 2004, 34 Year Old Jessica Palmer Died of Childbed Fever www.jessicastrust.org.uk/ 9 The House of Crime Louis Pasteur and The House of Crime Pasteur Pasteur became increasingly aware that infection was spread by physicians from sick to healthy patients. Pasteur Pasteur stated, "This water, this "This sponge, this lint with which you wash or cover a wound, may wash deposit germs which have the power of multiplying rapidly within the tissue....If I had the honor of being a surgeon...I would clean my hands with the greatest care...I would use only lint, bandages and sponges previously exposed to a temperature of 1300 to 1500 degrees.” Between April 1 and May 10, 1856, 64 out of 347 women in the Paris Maternity Hospital died of puerperal fever. The hospital, nicknamed the House House of Crime, was closed and the patients were transferred to a different hospital. Unfortunately, the disease followed these women and nearly all of them www.neonatology.org died. The Germ Theory of Disease Still Still doctors could not believe that puerperal fever was contagious and that they they transmitted it. Even Even after Pasteur’s identification identification in 1879 of Streptococcus Streptococcus pyogenes, a bacterium that he found in the blood of a woman with puerperal fever, his teachings related to the “germ theory of disease” did not catch on. Joseph Lister and Antiseptics Joseph Joseph Lister listened to Pasteur. Lister Lister (1870) began to apply antiseptics to antiseptics to the practice of surgery and the sterilization of surgical instruments caused a dramatic fall in post-operative ostdeaths from infection. Unfortunately Unfortunately Lister's ideas were also greeted with skepticism and skepticism it took nearly 30 years for "Listerism" to be universally accepted by medical practitioners. Eventually, Eventually, an antiseptic mouthwash was named after him. 10 Joseph Lister: Carbolic Acid as an Antiseptic Lister Lister was familiar with Pasteur’s work and Pasteur had suggested that there are three ways of getting rid of microbes: filter them filter out; heat them up or treat them heat with a chemical solution. The chemical first two were inappropriate for a human wound so Lister searched Li for for a chemical that would be harmless to people but would kill bacteria. Carbolic Carbolic acid (phenol) had been used to deodorize sewage and deodorize sewage Lister tried it as an antiseptic. Lister reduced infection when he used it to clean wounds, dressing, instruments and the hands of the surgeons. Joseph Lister’s Results were Ignored Surgeons and physicians were set in their ways. They probably saw Lister's excessive cleanliness excessive cleanliness and and his carbolic acid (phenol) sprays during surgery as a waste of time and effort. In addition, the spray burnt their hands and eyes. Lesson not Learned President President Garfield (1881) was a victim of an assassination attempt by Charles Guiteau (→). One One bullet grazed Garfield’s arm and the second bullet lodged in his back and could not be found back and could not be found. Garfield Garfield became increasingly ill over the next several weeks and was moved to a seaside community, in the vain hope that the fresh air might aid his recovery. Eighty Eighty days after he was shot, Garfield died of a ruptured spleen following pneumonia and blood poisoning. 11 Charles Guiteau Shoots President Garfield Charles Guiteau Bell http://www.law.umkc.edu/faculty/projects/Ftrials/guiteau/guiteauimages.html Who Killed President Garfield? Garfield Garfield probably would have survived his wound, had the doctors attending him considered germs germs more more important than miasma. miasma His His doctors inserted their unsterilized fingers into the wound to probe for the bullet and turned a 3 inch wound into 20 inch infected gash inch wound into a 20 inch infected gash. Guiteau’s Guiteau’s lawyers insisted that incompetent incompetent medical care had really killed the president, but it was not considered a legal defense and Guiteau was hanged. In In an ironic twist, the autopsy proved that the bullet was actually lodged in a protective cyst, far from where the doctors were looking. The doctors billed the government for $18,500. Hand Hand Washing in an ICU at a Children’s Hospital (1996) 12 Ethical Thinking and Dirty Hands Dirt-2004 Graduation Speech by President Jeffrey Lehman Robert Koch and His Testable Postulates The The medical establishment still was not sure whether the bacteria observed to be associated associated with a disease were the cause of the disease cause of or result or a result of being able to grow on or in an already pathological tissue or organ. In In order to overturn the skepticism involved with the germ theory of disease, Koch, a country doctor working in his home laboratory, proposed testable testable postulates. Koch’s Koch’s Postulates I. I. The bacteria must be present in every case where you find the disease. II. The bacteria must be II. The bacteria must be isolated isolated from the host and grown in pure culture. III. III. The specific disease must be induced into a healthy host when a pure culture of the bacterium is inoculated into it. Tuberculosis Killed 1 Out of 7 People "If the importance of a disease for mankind is measured by the number of fatalities it causes, then tuberculosis must be considered much more important than those most th th feared feared infectious diseases, plague, cholera and the like. One in seven of all human beings dies from tuberculosis. If one only considers the productive middlemiddle-age groups, tuberculosis carries away oneone-third, and often more." Cayuga Nature Center—Originally the Center— Cayuga Preventorium for Children with TB 13 Tuberculosis Using his postulates as a guide, Robert Koch identified the microbial cause of cause of tuberculosis: tuberculosis: Mycobacterium Mycobacterium tuberculosis (red (red→). He also identified the cause of rabies and anthrax. nobelprize.org/educational_games Alexander Fleming Discovered Penicillin By Accident Fleming Fleming (1928) noticed that, around a spot of mold which contaminated one of his cultures, the colonies of bacteria were dead. Fleming Fleming had discovered lysozyme in tears and saliva and was tears and saliva and was “…always on on the look-out for fresh substances lookwhich checked bacteria…” Fleming Fleming cultivated and transferred the mold to a broth. A week later, Fleming found that when the broth was diluted 800 times it completely prevented prevented the growth of many diseasedisease-causing bacteria, but not the one that caused tuberculosis. Howard Florey and Ernst Chain Developed A Method to Isolate Penicillin in Large Quantities and Gave the Laboratory Curiosity Practical Value Penicillin Help The Allied War Effort in WWII Residents of Peoria, IL, home to Merck were encouraged to bring moldy food to the plant to see if they could find better strains of Penicillium. Mary Hunt (1943), a worker at the plant, brought in a moldy cantaloupe that was infected with a Penicillium strain that allowed Merck to double their production. Selman Waksman: Antibiotics Selman Selman Waksman was studying the chemicals soil soil microbes used against each other in their own evolutionary evolutionary struggle struggle for existence. In In the course of this study, he isolated a couple of antibiotics. In fact, Waksman coined the term, antibiotic. He won the antibiotic Nobel Prize for his discoveries of antibiotics in 1952. 14 After After hearing of Fleming’s accidental discovery of penicillin, Waksman began a long-term, systematic and longassiduous program of research manned by a large group of manne researchers researchers to test 1000’s of soil microbes for their ability to kill the cause of tuberculosis, Mycobacterium Mycobacterium tuberculosis. Waksman Waksman and his team isolated an antibiotic from the soil actinomycete, Streptomyces Streptomyces griseus that was that effective in treating tuberculosis. effective tuberculosis Cure for Tuberculosis Discovered in LongLong-Term, Systematic Program of Research Selman Waksman “The Lord hath created medicines out of the earth; and he that is wise will not abhor them Ecclesiasticus abhor them. Ecclesiasticus, XXXVIII , 4” There is a Cure for Tuberculosis—But MultiTuberculosis— MultiDrug Resistant Germs Have Evolved.… Streptomycin Streptomycin was the first antibiotic that was used to cure tuberculosis. Currently long term Currently, long term treatment treatment with rifampicin and isoniazid, is used. isoniazid However, However, some Mycobacterium Mycobacterium have become resistant to resistant rifampicin and isoniazid, isoniazid, the two most effective frontfront-line antibiotics. MethicillinMethicillin-resistant Staphylococcus Staphylococcus aureus (MRSA), the “Superbug” Staphylococcus Staphylococcus aureus, which causes skin lesions, used to be skin killed by penicillin and penicillinpenicillinlike antibiotics. In In 1961, “superbugs” were “superbugs” di discovered that were resistant to th res these antibiotics. The The superbug was often acquired in hospitals that use many antibiotics. The The superbug is easily spread through anal intercourse, and in January 2008, it was discovered to be spreading rapidly through gay communities in Boston and San Francisco. Epidemic FluoroquinoloneEpidemic of Fluoroquinolone-resistant Clostridium Clostridium difficile Results from the Overuse of Antibiotics and Insufficient Hand Washing C. C. diff causes diarrhea and pseudomembranous colitis. C. C. diff spores enter the body through the spores fecalfecal-oral route and grow in a colon when antibiotics have suppressed the normal pp disease fighting bacteria in the colon. H2H2-receptor antagonists and proton pump inhibitors that suppress the production of gastric acid increase the likelihood that the spores will reach the colon alive. C. C. diff is usually a nosocomial infection. That is is, it is transmitted by healthcare workers from an environment contaminated with fecal matter. www.cdc.gov www.youtube.com 15 Antibiotic Resistant Bacteria As As antibiotics were used more and more, bacteria developed resistance to resistance the antibiotics and antibiotics became less effective in fighting disease. Consequently physicians Consequently physicians prescribed prescribed more and more antibiotics and the bacteria became more and more resistant, etc. etc. etc. Bacteria Bacteria resist antibiotics, by preventing their uptake, or by producing enzymes that degrade, modify them or pump them out. Bacteria Gain Resistance Genes By Mutation and Gene Transfer Note that many soaps contain antibiotics, animal feed often contains antibiotics and antibiotic resistance genes are used to manufacture genetically-engineered food. Bioterrorism: Fighting Wars With and Against Microbes http://www.bt.cdc.gov/bioterrorism/ http://www.bt.cdc.gov/bioterrorism/ http://www.fda.gov/oc/bioterrorism/ http://www.fda.gov/oc/bioterrorism/ bioact.html http://www.nlm.nih.gov/medlineplu http://www.nlm.nih.gov/medlineplu s/biodefenseandbioterrorism.html http://www.health.state.ny.us/envir http://www.health.state.ny.us/envir onmental/emergency/index.htm http://www.nyc.gov/html/doh/html/c http://www.nyc.gov/html/doh/html/c d/wtc8.shtml Epilepsy: A Neurological Disease In In ancient times Hippocrates thought that epilepsy had a physical cause, but others called it the “Sacred “Sacred Disease” and thought that it was caused by supernatural beings. The cause of epilepsy in 75% of The cause of epilepsy in 75% of epileptics epileptics is unknown. A chemical imbalance, brain tumors, strokes or a head injury may result in head localized localized damage or scar tissue in the brain that causes epilepsy. The The symptoms of epilepsy depend on where in the brain the damage occurred. Epilepsy: Generalized Seizure Seizures Seizures are initiated by an electrical electrical disturbance from the damaged brain tissue. When When the electrical di disturbance passes throughout the brain, a person may experience a generalized generalized seizure and may lose consciousness for 30 seconds (petit mal) or their whole body may spasm (grand mal). Epilepsy: The Body May Influence the Mind When When the electrical disturbance is localized, people may experience partial partial seizures. Depending Depending on where in the brain the electrical the brain the electrical disturbance disturbance is localized, a person may hear, see, smell or taste things that are not real. They They may also seem drunk, feel afraid, angry, happy or sad for no reason. 16 StressStress-Related Diseases In In 1918, more people died of the flu than fighting World War I. With With the exception of AIDS, few people in developed countries die of infectious diseases anymore. In In developed countries, most people die of stressstressrelated diseases, high blood pressure, heart attacks and mental illness. According to Ivan Pavlov, Walter B. Cannon, Hans Selye and Robert Sapolsky, the Mind Can Influence the Body Prolonged Stress Causes Disease Walter Walter B. Cannon showed that strong emotions influence body functions through adrenaline which causes an adrenaline which allostatic allostatic transition in the body from the rest and digest stage to the fight or flight (4Fs) stage. Adrenaline causes Adrenaline the heart to pump faster, increasing the blood pressure. Hans Hans Selye showed that steroid hormones also participate in the stress response in the stress response. Cortisol increases Cortisol increases the energy supply by causing breakdown of muscle and nerves. Aldosterone increases Aldosterone increases the supply of oxygen to the necessary muscles by increasing the blood pressure as a result of the stimulation of sodium re-absorption. reHowever, However, if stress is kept up for prolonged times, the prolonged times, unregulated degeneration of muscles and nerves and the increased pressure in the circulatory system lead to strokes, heart attacks, kidney disease and mental illness. High Blood Pressure (Hypertension) The Discovery of Genetic Diseases Inborn Factors in Disease Archibald Archibald Garrod (1899) studied the color of urine in various people. The urine The urine of people with alkaptonuria turns black when it is exposed to air. Alkaptonuria Alkaptonuria was thought to be caused by a bacterial infection, but Garrod realized bacterial infection, but Garrod realized that that alkaptonuria was not contagious. Garrod Garrod (1901) found that the parents of children with alkaptonuria were healthy but he found they were also first cousins. first With With the rediscovery of Mendel’s Laws in 1902, Garrod realized that alkaptonuria was a genetic disease that expressed genetic itself in homozygous recessives. Alkaptonuria 17 Another Genetic Disease Archibald Garrod: Genetic Factors: Inborn Errors in Metabolism Phenylketonuria Our genetic destiny can be modified by diet. Phenylketonuria and alkaptonuria can be managed by eating foods low in phenylalanine. Treatment of Genetic Diseases The genetic factors can be controlled through: – Diet (e.g. phenylketonuria, alkaptonuria) – Drugs that regulate body chemistry (MAO inhibitors or re inhibitors or re-uptake inhibitors) inhibitors) – Injections of proteins that the body would normally make (Human Growth Factor) – Gene therapy (Adenosine deaminase) – Detect genetic predispositions to disease (genetic testing) – Design “custom drugs” (pharmacogenomics) based on individual genetic profiles Cancer Cancer Cancer Cancer results when a cell becomes transformed and then divides in an out-ofout-ofcontrol manner to form a tumor tumor. If the tumor is malignant If the tumor is malignant, some of the daughter cells invade the rest of the body (metastasize) and continue to divide until they kill the person. Cancer Cancer will only occur if the cytotoxic T cells of the immune system do not recognize the transformed cell and destroy it. Cancer Caused by Oncogenes Some Some viruses, like the Rous (1911) sarcoma virus of chickens, carry cancer-causing cancergenes, known as oncogenes. oncogenes Many Many normal genes have the ability to become oncogenes become oncogenes. J. J. Michael Bishop and Harold Varmus found that these proto-oncogenes code for protoproteins that regulate cell division and when a mutation occurs in these genes, they transform into oncogenes. Consequently, oncogenes. Consequently, cell division becomes unregulated and unregulated cancer cancer results. Oncogenes Oncogenes Stimulate Cell Division Mutations in proto-oncogenes result in out-of-control cell division. 18 Activation of a Gene Leads to Cancer Chronic Chronic myelogenous leukemia (CML) results when chromosomes 9 and 22 break in a stem cell in the bone marrow and then undergo reciprocal reciprocal translocation. The translocation causes gene The translocation causes a gene that inactive in that is inactive in chromosome 9 to become active in chromosome active in 22 (“Philadelphia chromosome”) and the active gene results in active leukemia. This This shows that the expression of a “trait” is determined by the location location of a particular gene. ras-Oncogene The ras protoThe ras proto-oncogene typically participates in a growth factor-stimulated factorsignal transduction chain that initiates the formation of protein formation of a protein that that stimulates cell division. The The oncogene can activate the signal transduction chain in the absence of a stimulus (growth factor). Tumor Suppression Genes Tumor Tumor suppression genes code for proteins that inhibit inhibit cell cell division. Cancer Cancer occurs when mutations occur in the tumor th suppression genes. Cancer Cancer also occurs when genes inserted by gene therapy disrupt tumor suppression genes. The Blood and the Disease, Orit, age 6 (leukemia) Tumor Suppression Gene A mutation in a tumor suppression gene results in out-ofout-ofcontrol cell division. p53p53-Tumor Suppression Gene The p53The p53-tumor suppression gene typically participates in a growthgrowthinhibiting factor-stimulated factorsignal transduction chain that initiates the formation that initiates the formation of of a protein that inhibits cell division. The The mutant p53 gene codes for the formation of a transcription factor that cannot trigger transcription of the gene that codes for a protein that inhibits cell division. Colon Cancer The development of cancer requires several mutations in the same cell, including mutations in protoprotooncogenes, tumor-suppressor genes and genes tumorinvolved in DNA repair. DNA 19 Cancer and the Curative Effect of Surgery Surgeons Surgeons once only removed “stones” and believed that it was impossible to perform operations on the internal organs. Thus many diseases resulted in death. The The first ovarian cancer surgery was performed as an “experiment” by Dr. Ephraim McDowell (1809), a backwoods physician in his home in Kentucky after he examined examined Jane Crawford, who thought that she was pregnant with twins. Dr. Dr. McDowell diagnosed her as having an ovarian tumor and he successfully removed the ovary, which contained a tumor that weighed 22.5 pounds. The The fact that this “experiment” was successful eventually led to the idea that internal surgery could be used to cure diseases and experimental procedures continue to be used today. Ephraim McDowell: Internal Surgery Ephraim Ephraim McDowell "Having never seen so large a substance extracted, nor heard of an attempt, or success attending any operation such as this required, I gave to the unhappy woman…information of her dangerous situation…. The tumor tumor…appeared full in view, but was full in view but was so so large we could not take it away entire…. We took out fifteen pounds of a dirty, gelatinous looking substance. After which we cut through the fallopian tube, and extracted the sac, which weighed seven pounds and one half…. In five days I visited her, and much to my astonishment found her making up her bed.” The Cancer Genome Atlas (TCGA) (note the letters in the acronym) For For $1.5 billion, TCGA will make a list of mutations (SNPs) in the DNA found in primary tumors of SNPs) patients with lung, brain and ovarian cancer that differ from the DNA found in healthy cells of the same individuals. The CGA hopes to design anticancer drugs that will bind to the proteins anticancer drugs that will bind to the proteins coded coded by genes with mutations. Research Research has shown that there are hundreds of mutations in the DNA of tumors. It was simplistic, naive and poor science to think that there were only a few mutations in tumors. We do not know if the mutations the were found are cancer-causing. cancer-causing. http://cancergenome.nih.gov/about/index.asp h 20 Carcinogens: Environmental Causes of Cancer There There are chemicals and types of radiation in the environment that cause cancer, typically by inducing mutations in genes that regulate cell division or DNA DNA repair. Tobacco, Tobacco, estrogen, sexually transmitted viruses (HPV) and the ultraviolet light in sunlight are carcinogens that increase the risk of lung, lung, breast, cervical and skin cancer, respectively. Environmental Estrogens Were Discovered By Carlos Sonnenschein and Ana Soto For your own Health, Be Skeptical Skeptical of Advertising 21 Your Baby will Get Nicotine if you Smoke while you are Pregnant 22 An Original Take on the War on Drugs “It is the height of hypocrisy for the United States, in our war against drugs, to demand that foreign nations take take steps to stop the export of cocaine to our country while at the same time we export nicotine, a drug just as addictive as cocaine, to the rest of the world.” www.opensecrets.org-tobacco Reducing Health Risks We have the ability of reducing health risks due to environmental factors at at little cost by being hygienic, hygienic, eating well, maintaining an environment that provides clean air, clean water and clean soil, not smoking and learning to cope with stress. Medicalization: Medicalization: Scientific Progress or Disease Mongering? Medicalization occurs when we have the perception that nonmedical conditions are medical problems and medi nondiseases nondiseases are diseases— diseases— just watch the ads on TV. Which things are medical establishment right about and which things will turn out to be incomplete or wrong? 23 Advice from Ruth Hubbard (1997) “It may be a new idea for us to regard a scientist’s or physician’s recommendations as skeptically as we skeptically as do those of other kinds of salespeople, but we need to do just that. To keep control control of this tangled situation, we must learn what questions to ask, and we must not accept that the answers are too complicated for us to understand. We need to be sufficiently well informed to be able to evaluate critically what the ‘experts’ tell us, so that we can make our own judgments about what tests and what information are likely to benefit us.” Geneticization: Geneticization: Scientific Progress or Gene Mongering? Geneticization, Geneticization, a term coined by Abby Lippman, Lippman, an epidemiologist and Cornell graduate, is an outlook outlook that places primacy on “genes, alleles or SNPs” and ignores the SNPs” social, political, economic and the other biological factors that shape our lives and influence our health. Newgenics: Pre-Implantation Genetic PreTesting To reduce the number of diseased individuals on Earth, eliminate embryos with haplotypes that are haplotypes that correlated with risks correlated with risks of getting various diseases. diseases 24 Eliminate Disease “We “We are pleased to…offer African patients the option of screening and preventing WITH NEAR 100% certainty, the occurrence of sickle cell disease in their pregnancies…. disease in their pregnancies…. This This combination of sciences offers the opportunity for African couples to both CHOOSE THE SEX OF THEIR BABY and assure that sickle cell disease is not present in the new pregnancy.” Eliminate Sickle Cell Anemia The Promises and Perils of Designer Babies http://www.genetics-and-society.org/ Death People People die, even so when a loved one dies, it stinks. You feel a pain like you have never felt before. But, But, if no one died, there would be no room on the planet for anyone else. You You never know when it will happen, so to the best of our ability we have to keep each relationship (including the one with our self) in the condition in which we would have no regrets if it were to end suddenly due to death. Rodney Dangerfield recites Dylan Thomas's Do not go gently in to that good night From Parlour to Living Room When When death from disease was a commonplace and unpredictable, the recentlyrecently-deceased were laid laid out in the parlour while the funeral arrangements were being made. With With the decrease in the death rate from disease, the parlour parlour was replaced with the “living room.” 25 The Accidental Discovery of X-Rays XWhen Wilhelm Roentgen (1895) was using a cathode-ray tube, he noticed that a nearby piece of barium platinocyanidein gave off light. He guessed that the electrons striking the tube's glass wall formed radiation that caused the fluorescence. He called the mysterious radiation, X rays. He then found that the X rays penetrate living tissue, except bones, and produce images on photographic plates. Testing and Early Diagnosis Chest X-Ray (Pneumonia in Upper Right Lobe) X- Chest X-Ray (Pneumonia Resolving in Upper XRight Lobe) CAT (Computer Assisted Tomography) Scans CAT scans combine X ray images with a computer. The CAT scan takes many ray pictures many X ray pictures of the same area produced by a rotating X ray tube. The computer then puts the information together to create a cross-sectional image. Inject Contrasting Agents Into Blood Stream to Visualize the Bloodstream in a CAT Scan 26 Ultrasound Ian Donald used a “speaker” and a “microphone” to generate and receive sound waves sound waves differentially differentially bouncing off materials with different viscoelastic properties to create an image of a baby inside the womb. Ultrasound Ultrasound Positron Emission Tomography Radioisotopes (11C, 15O, that emit positrons (antimatter form of electrons) are attached to specific molecules (e to specific molecules (e.g. glucose) and injected into the body. PET creates an image by detecting the gamma rays given off when a positron (antimatter) collides with an electron (matter) and they annihilate. 18F, 75Br) CAT, CAT, PET, CAT+PET Isotopes Isotopes attached to glucose are taken up by fast growing cells making PET a good imaging technique for detecting cancer. Magnetic Resonance Imaging (MRI) MRI MRI uses a powerful magnet and radio signals to "see" inside the body. MRI MRI is helpful in looking at soft tissue, including organs, muscle, cartilage, ligaments and tendons. MRI MRI can identify and show the difference between healthy and unhealthy tissue. With With MRI, it is often possible to diagnose disease at very early stage. Because most disease are better treated when found early, MRI scans are becoming increasingly more popular. nobelprize.org/educational_games 27 Endoscopy Large Intestine with Small Polyp Capsule Endoscopy (Pillcam) http://www.givenimaging.com/Cultures/en-US/Given/English/ 28 ...
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