Medical Firsts Adler

Marcus Varro

-116-27 BC, wrote 620 books in his lifetime, only surviving book is 3 volume dialogue addressed to wife about farming -"On Farming"- first to discuss germ theory of disease- certain minute creatures that cause serious disease, common in swampy regions so told his wife where to grow -was a soldier under Julius Caesar, Mark Antony burned his private library so we don't have any of his books -"the most learned of the romans"- wrote on history, religion, philosophy, medicine, math, law, etc. -his idea did not spread because the romans did not think highly of medicine -he was motivated by the desire to help mankind, he progressed medicine because he was observant and learned from his surroundings, upsetting that his greatest discovery lay dormant for so long (mentioned again in 1546)

Ibn al-Nafis

-1210-1288, Damascus to Cairo -cleared up confusion that Galen started over movement of blood from atria to ventricles to lungs for aeration & back to heart to be pumped thru body -headed a hospital in Cairo, appointed by the king, left all of his belongings to the hospital when he died -great controversy over dissection, some suspect he used it (despite Islam) -"felt free to to make his own observations and to correct all the previous research" -determined not to believe any past claims unless proven firsthand -disagreed with Galen's model of the heart and came up with the model that we basically believe today -Disproved Galen's claim of invisible pores (200 AD) but others did not confirm til 1500 AD -first to understand and describe pulmonary circulation -corrected Galen's idea on how blood flows to brain and Ibn Sina's description of 5 and 6 cranial nerves -al-Nafis ideas breakthrough on the heart were not discovered until 1924, before him, Servetus presented his version in 1556 (strikingly similar to Nafis) which denied the church so he and his book were burned, Colombo also published accurate description in 1558 -western historians deny that he al-Nafis performed dissections and also denied that his findings influenced Servetus and Columbo -mystery whether or not his discoveries translated from Islam to Christianity, but it solid fact that he discovered 3 centuries before anyone else 1. Goal was to provide medical care to all ppl (rich & poor) 2. Did not think true scientific investigation would undermine allah's authority 3. refused to accept anatomical/physiological/medical belief w/out testing it (like Descartes)

Paracelsus

-1493-1541 -very religious but a very bad temper, carried around a sword, cured many people that other doctors couldn't but couldn't fix himself and died at 48 -wanted to disprove Galenic medicine and said that each disease has unique cause and cure and chemicals could make drugs for them -doctors should treat rich and poor alike - Pioneered use of chemicals & minerals in medicine -where he received his formal education is unknown, he started in Germany but thought it was a party school, went to Italy but they still taught Galen's medicine -did not think anatomy was helpful, need to know the living not the dead -army doctor for a while and then called to Switzerland to heal Johannes Froben, fixed him and appointed him city physician -created a manifesto that declared war on medicine (didn't support Hippocrates or Galen) and angered other physicians -tried to ban him from teaching but he argued, lectured in German and convinced people to distrust medicine of the time -a student posted pamphlets making fun of him, school did nothing, charged a poor man a lot of money, man didn't pay, court did nothing, Paracelsus argued and eventually fled -Hermetical views were that sickness and health in the body relied on harmony of man (microcosm) & nature (macrocosm) -major contributions to toxicology (poisoning of body from outside of body) & psychotherapy -doctors should treat rich and poor alike, each disease has a unique cause and cure, chemistry may be used to create pure and potent drugs -humans must have certain balances of minerals in there bodies, certain illnesses of the body had remedies that could cure them -first to ask what made a medication effective, first to attack Galenic medicine, inventor of medical chemistry -first to view diseases as specific entities, each stemming from a specific external source (key step on path to germ theory) -deeply flawed but had extraordinary vision -believed all mysteries could eventually be understood and all disease cured, "we shall be like gods" -"did not seek small, temporary truths, was driven to find great eternal ones"

John Snow

-1813-1858 -he was sent to help those infected with cholera in England but many died, during his apprenticeship he became a vegetarian and gave up alcohol, lived a simple life with no wife and few friends, focused on his studies -he was described as caring, but his mind was too full to just stick to patient care, so he researched, his first paper was on air pump to resuscitate newborn babies -heard of ether use for anesthesia in America and tested it on animals, himself, and dental patients, then hired by surgeon Lister to be anesthesiologist -Cholera came back to England and most blamed in on bad air and humor imbalance, but Snow believed it was a disease caused by moving living things that needed time to incubate in humans -patients often became dehydrated, so Snow eliminated symptoms using IV fluid, but without antibiotics he could not cure it -he realized the feces of sick spread into the water and those who drank it became infected, so he published and gave up his practice to prove this in his own neighborhood of Soho -he went door to door near the many deaths that occurred near the Broadway water pump, and found that those who died used it, but death skipped the houses that did not use it -he took it board of parishes and they removed the handle from the pump, and the disease subsided, there is now John Snow Pub honoring him at the corner -he found a neighborhood that used two different water sources and used this as a control to eliminate the ideas of income and geography -people still believed in humors and miasmas, but they began purifying water, those without access to pure water are still at risk of cholera -Snow died of a stroke while working on a book on anesthesiology -Robert Koch found the microbe that caused cholera and it matched Snow's description perfectly, his idea that living things caused communicable diseases was correct and proved by Koch and Pasteur in germ theory -"even though he wouldn't have joined us, we owe Snow a quiet toast" -Adler

Dmitri Ivanovsky

-1864-1920 -at the time people thought all disease was caused by microbes -Russian graduate student of botany studying disease of tobacco plants, growth was stunted by tobacco mosaic disease (one of his teachers was Dmitri Mendeleev), juice from infected could transmit disease to healthy plants -Ivanovsky put juice through Chamberland candle, fine filter made of porcelain, designed to stop bacteria, and the tobacco disease still got through -thought toxin or spores from microbe were slipping through -Beijerinck worked with Mayer, first ones to observe mosaic disease, but did not know origin, also discovered it could pass through Chamberland filter and also believed spores or toxins, so he tested: heated and no longer infected, spores would've survived, able to reproduce so not toxin, noted only multiplied in places plant cells multiplied, decided it was a small, soluble molecule or a fluid water, eventually proposed a "contagium vivum fluidum" and saw it entering cell protoplasm and reproducing by the action of the cell -Beijerincks papers came to Ivanovskys attention, wrote to claim priority on passing through filter, he agreed, criticized agar experiments, and believed virus had to me solid particle -but still believed they were pores, Beijerinck was the first and only for a long time to think viruses were something different -both worked to understand something new and got contrasting results, Beijerincks contagium acted like a living thing (infect other plants, cause disease, reproduce) but not any living thing they knew because it could pass through filter -B came closer than I imagining something bizarre enough, controversial but inspired other research -many people showed that human and animal diseases were caused by virus and not bacteria, and in 1925 Felix d'Herelle at Pasteur Institute discovered bacteria-killing viruses, bacteriophage -Wendell Stanley crystallized tobacco mosaic virus proving it was a molecule and determined they were made or protein and later Bawden and Pirie discovered RNA in it -this became in important 16 years later in 1953 when Watson and Crick discovered structure of DNA and NA were carrier of genetic info -1950s saw polio and Sabin vaccine, smallpox in 1977 -we now know a lot more, but as AIDS tragically shows, we do not know enough, AIDS soon may pass the Black Death as the worlds greatest natural killer

Margaret Sanger

-1879-1966 -known as the Mother of the Pill, fiery social activist, nurse, devoted life to the fight for birth control -mother had 11 children and 7 miscarriages, Margaret blamed her father -worked her way through nursing school in NYC, grew up poor, married in 1902, focused on OB/GYN -got bored with the housewife life and became an activist, started a newspaper called The Woman Rebel and in it she coined the term Birth Control, believed women had the right to know how to prevent pregnancy -federal and state laws prohibited publication on BC info, so only MDs could give the rich the info -many women who didn't want more children for illegal abortions and died from them -The Woman Rebel was banned and in 1914 Margaret was indicted on indecency charge, punishable by 45 years in prison -she fled to England (left kids with husband) and realized clinics where women could receive care and guidance like she saw in the netherlands was necessary -came back to US when husband was jailed and she used her trial to publicize the cause, and bc of negative publicity, the gov dropped it -she opened a birth control clinic and her and all women there were arrested and 464 case histories were confiscated, but her tactics led to another victory: NY state court of appeals broadened definition of disease to incorporate risks of pregnancy so the process of legalizing contraception began -she fought tirelessly and in 1937 overturned comstock act, allowing contraceptives to be sent in mail -still the only offers were condoms and diaphragms so Sanger wanted something easier but needed a scientific breakthrough and money -money came from Katherine Dexter McCormick, one of first female graduates of MIT, husband had a lot of money but was schizophrenic, she fought for women's right to vote and got husbands estate after his death and in 1950 wrote to Sanger about BC prospects -Sanger got in touch with Gregory Pincus, Cornell and Harvard graduate studying mammalian reproduction, was Harvards youngest associate professor, wrote book in 1936 The Eggs of Mammals, but he went too far into controlled reproduction (in vitro rabbit eggs) and stirred up a media storm, Harvard deemed him a pariah; denied him tenure and sent him packing -he opened Worcester Foundation for Experimental Biology, worked with GD Searle Pharmaceutical firm for breakthrough medications -Sanger and Pincus met in 1951 and promisingly discussed contraceptive, Sanger and McCormick visited the lab and Pincus turned the lab to that goal -wanted an oral contraceptive for women, couldn't get government funding or Planned Parenthood, so McCormick gave an estimated $2 million -in 1921 Haberlandt transplanted ovary from pregnant rat into not pregnant rat and it was unable to ovulate, thought hormonal contraceptives for women was possible -Corner and Allen traced it to corpus luteum that produced progesterone and later Doisy discovered estrogen -3 physiologists at Penn injected rats with progesterone and they did not release eggs -1945 Fuller Albright predicted birth control by hormone therapy -Pincus went to Russell Marker for cheap progesterone, organic chemist at Penn, he and partners began working on it but had falling out and was replaced by Carl Djerassi -came up with powerful progesterone analogue that could be taken by mouth called norethindrone which later proved to be key ingredient of the pill -Frank Colton of GD Searle created similar norethynodrel -Pincus went to John Rock a catholic physician who was very liberal on birth control (others called for his excommunication) and he could "get away with anything" because of looks and personality -Rock had been injected inferior women with Markers progesterone and got rid of period, when it came back they had heightened fertility -Rock gave volunteers Colton's norethyndrel and Pincus and Rock realized they had a workable birth control pill -needed to test it much more to get FDA approval so went to puerto rico with prematernity clinics and women rushed to try it -physician Edris Rice-Wray saw it prevented pregnancy in those who took it properly and those who stopped had normal babies -30 times more effective than condoms but had symptoms that she said made it not worth it, but tested a placebo and it had similar effects -FDA surprisingly approved with little fuss formally on May 11, 1960 -GD Searle made a lot of money along with their supplier Syntex and stockholder Carl Djerassi -baby-book generation were maturing after WWII and GD, and became era of sex, drugs, and rock and roll -helped liberate women from role of wives and mothers -"For the first time in history, women seized control of their reproductive lives, challenging Sigmund Freud's chilling observation 'Anatomy is destiny.'" -The Pill and morning after pill have significantly lowered abortion rates -research at oxford shows promise of male contraceptive -there are side effects and the pill is still controversial -catholic church still objects to it even tho a lot of them use it, women's health clinics are terrorized, and there's an assault against Roe v. Wade that gave women the right to choose abortion -millions still lack access to accurate info and practical means of birth control -for too many women biology remains their destiny, and their miseries remain "as vast as the sky" (Sanger)

Alexander Fleming

-1881-1955 -modest, reticent, hid brilliance and drive from everyone -came across drive to defeat infection while treating battlefield wounds in WW1 -discovered that normal antiseptic techniques did not kill all bacteria but damaged tissue and inhibited white blood cells, showed that removing as much dead tissue as possible and cleaning with saline solution minimized infection and increased bodies defense mechanisms -attributed much of success to luck, remarkably observant, amazing in school, top score on med school exam, chose st mary's in london, earned top scholarship, but also loved sports (water polo, golf, marksmanship), handsome but very shy, inscrutable -1921 discovered nasal mucus was killing bacterial colony, called it lysozyme, discovered human blood, tears, milk contained antibacterial agents, and so did animals and plants -1928 noticed that staph colonies near mold dissolved, grew a bunch of mold and saw it could kill a lot of kinds of bacteria, and the juice of the mold even when extremely dilute could kill bacteria -presented to Medical Research Club but nobody seemed to care, he was hurt that nobody noticed his discovery, wrote paper in British Journal of Experimental Pathology about Penicillin, antibacterial substance -believed injections could stop diseases, mentor Wright didnt like the idea and told him to drop it but he disobeyed -published in 1929, proved in 1936 that i worked better than sulfa drugs, but nobody took his work seriously, and had to leave britain in 1939 because of war -Howard Florey (1898-1968), Australian pathologist, worked with Ernst Chain (1906-1979), studied natural antibiotics, read Flemings paper on penicillin, worked with Norman Heatley -were able to make it into a much stronger powdered salt, on May 25, 1940 they injected it into 4/8 mice with streptococci and they survived while the others died -"It looks quite promising" -Florey -tested it on a few desperate humans and then published in british medical journal, the Lancet -Fleming learned of this and went to visit him and they were shocked, Chain thought he was dead -said it was the happiest surprise of his life -encouraged by Rockefeller foundation, Florey and Heatley went to america in attempt to manufacture on a large scale -Northern Regional Research Lab, Peoria, Illinois, better purification techniques, made one million times more powerful than original juice, and 10 thousand times more effective than sulfa drugs -none of them attempted to patent "penicillin" believing it would h available to everyone and not expecting it to become commercial trademark -by D-day, June 6, 1944, all Allies were being treated -antiseptic procedures by Semmelweis drastically lowered death by childbirth, penicillin lowered it even more -now researchers and bacteria are in an arms race (resistance), most promising approach seems to lie in sequencing genome of disease causing bacteria and helpful microbes -understanding at molecular level how bacteria protect themselves offers our best chance to stay one step ahead of these superbugs

Soranus

-1st century AD -"The birthing doctor" --> brought practice of midwifery into medical fold, awakened physicians to women's unique medical needs -1st to elevate obstetrics and gynecology to status of legitimate medical specialties by building off anatomy of Herophilus - Trained as a Methodist physician---> rejected Hippocratic theory of humors; atomists and skeptics, believed in pores in the body that when too closed or too open made you feel sick -Argued that doctors didn't need to know much about anatomy, physiology, or pathology -Put his trust in what he saw --> KEEN OBSERVER, noticed that female anatomy opened a new realm of disease for them -he raised the art of differential diagnosis to a new level and outgrew the methodist views -wrote about how to birth a child, created podalic method, and wrote about menstruation, first to mention what we call PMS -Gynaecia - compendium on the medical treatment of women -1st to write about diagnosis and treatment of psychiatric problems like mania &melancholia -Described how to handle breech birth -Authored 1st bio of Hippocrates -his ideas were lost, "the rational medicine of antiquity went through a long process of being diluted, or rather spiced up, with more magic ingredients and more exotic recipes" -OBGYN not brought back until 16th century renaissance

Erasistratus

-330-255 BC Alexandria -1st Physiologist -Primarily interested in knowing HOW ORGANS WORKED AND WHAT THEY DID -influenced by atomistic view and tried to describe mechanics of organs -Correctly identified heart as origin of both arteries and veins ---1st to understand heart= pump, and 4 valves; came closer than anyone would for 2000 yrs to understanding blood flow/circulation -determined that arteries and veins must communicate- anastomosies, now called capillaries, even though he could not see them -then people beleived veins carry blood from heart (does when body is dead) and arteries contained pneuma- air/spirit -after him is was not possible to dissect human bodies, so advancements in anatomy stopped, and their students stopped advancing and began disputing -studied under Chrysippus in the competing Cnidian School -him and Herophillus advanced anatomy and surgery -Christianity took over and they destroyed the library and the last scholar and valued piety over inquiry, sanctity over science

eradication of smallpox

-Ali Maow Maalin was the last person to infected with smallpox in 1977 and he survived =Edward Jenner created the vaccination in 1796 and knew if enough people used it they could eradicate it, and some countries did this in late 1890s-1900s, but in 1966 many countries still did not spread the vaccine and lost millions of people -during the cold war the soviet union suggested a five year plan to WHO to eradicate it by vaccinating everyone, and the soviets donated over 140 million doses a year -WHO did not do very well and it took more than a decade for this plan to work, many were still skeptical -a joint CDC-AID initiative allowed vaccinations to occur much more quickly and helped other parts of the country to rid the disease, Candau believed it would fail so he sent Henderson to be in charge in Geneva so he could be to blame when it failed -Henderson knew he needed to appeal to each country in a different way, and he was careful on who he hired. some countries had little doctors or clinics, and some did not want the vaccine. WHO also provided no help in encouraging countries to cooperate, so Hendersons can do attitude angered beaurocrats who were used to covering up problems, not solving them -at first it was difficult to travel with and get the vaccine to work bc you rubbed it on the arm and poked a needle 15 times hoping it would take, then Ben Ruben and Gus Chakros invented a new way to inject with two needles that held just enough vaccine, and almost anyone could learn to use it, making it much more portable -a new method was created to only vaccinate areas with outbreaks and not just everyone, championed by William Foege, called E-Squared, eradication escalation -he decided they needed to create a system to find, identify, and report every case, but this created a tidal wave of reporting from 1 to 100% which local health officials did not like, then workers would go to and quarantine (quickly) -he first applied it in Nigeria where he realized it ran in seasonal cycles (lowest in October) so that would be the best time to attack the disease -they were only able to vaccinate a small fraction of people in Nigeria, but it worked and they cleared the country of the disease -the Americas were eradicated in 1971 with the last country being Brazil -in 1972 Ethiopia, India, Pakistan, and Bangladesh were the only remaining countries, India being the worst -when WHO realized Indian doctors were encouraging people not to report the disease, WHO workers went door-to-door and vaccinated anyone in a 5km radius of an outbreak -it took enormous effort to rid India of the disease, but on July 4, 1975, the last patient was released from the hospital -Bangladesh was rid in 1975, and left were Ethiopia and Somalia, where health workers faced many obstacles including violent resistance -in October 1977 the last man survived the disease, Ali Maow Maalin -the virus is still stored in two high security facilities in Vektor in Siberia and the U.S. Center for Disease Control and Prevention in Atlanta, and they have began experimenting with it for diagnostic tools, drugs, and better vaccines in the case of bioterrorism, and as long as the virus exists it could be realesed into the world again

Organ Transplantation

-Christian Barnard (1929-2001) performed the first organ transplant on a patient who needed a heart in 1967 -stories of skin grafts for noses and a leg transplant -John Hunter (father of surgery) performed transplants on chickens to experiment -Alexis Carrel figured out how to move organs around in a species, but realized it always failed between species, discovering rejection -Karl Landsteiner discovered there were different blood types and transfusions only worked if they matched in early 1900s -scientists discovered the immune system is designed to establish between itself and foreign objects, Macfarlane Burnet discovered clonal selection theory- white blood cells have many recognizing agents and when the object is foreign the cells multiply to attack as immune response -Charles Hufnagel tried to save a dying woman by transplanting a kidney in her forearm and it worked as soon as blood started flowing to it, it only lasted a few days but it gave her time for her kidneys to start working again and she survived -John Gibbon made first heart and lung machine so surgeries could last longer, Rene Favaloro did first bypass surgery at Cleveland Clinic -rejection became a barrier but doctors discovered immunosuppresants to use during surgery, then Joseph Murray did a kidney transplant between identical twins and it worked -by the time Barnard did the first heart surgery, 3/4 kidney transplants survived -Christiaan Barnard grew up in south africa with hardworking parents and little money, he became a doctor and worked in general practice but then got money to got to Minnesota to get PhD and surgical credentials -gave a dog two heads in experiement in south africa, then went to the americas to learn about kidney transplant and rejections, then worked with Richard Lower, a colleague of Shumway and learned how to animal heart transplants -got money from Groote Schuur hospital for equipment and meds and developed a protocol to match organs, did many animal heart transplants then human kidney transplant in 1967 successfully, developed an ethical way to determine a donor dead -determined to do first successful heart transplant but there was a lot of competition, but his confidence and determination got him over that -the patient came: Louis Washkansky, he had a series of heart attacks and was given a few weeks to live, so he was willing to try the transplant -Denise Darvall was the donor, she was injured in a car accident and was pronounced brain dead on Dec 3, 1967 -in all the heart had been stopped for 3 hours, but when Barnard gave it an electrical shock, it began to beat normally again -he became instantly famous even though the patient died 18 days later of respiratory failure caused by bilateral pneumonia, and he was sent to America to celebrate with President Johnson -Barnard performed another one and the patient survived for 19 months, so more than a hundred were performed, but the poor results drove people from the field and in 1971 there were only 9 heart transplants worldwide -Shumway at Stanford did not give up and did a lot of research to improve the process -by 1989 there were 100 transplant teams and 85% of patients survived -organ transplant is now common in the US, with 25,000 expected to be given life from it in a year, but only 1/3 of people needing organs will get them because of the shortage

Anesthesia

-George Wilson underwent surgery a year before anesthesia and wrote of the horror Leading scientists around anesthesia: Paracelsus, crawford long, horace wells, john morton, william morton, charles jackson -many people would choose death over surgery -ancient cultures knew mandrake, poppy, datura, opium could reduce pain/induce sleep -Humphry Davy wrote about the abiltied of Nitrous Oxide, and Faraday on sulfuric ether -Nitrous oxide and sulfuric esther used in early 1800s for partying in U.S. but the idea to use it for surgery did not spread -1st american to experience ether's effects was crawford long, he removed a tumor from a friend after giving him ether and he felt no pain, peformed more surgeries but did not publish for 7 years -next = horrace wells; saw that a man at traveling Nitrous Oxide show that a man had not noticed his bleeding leg, ended up using on self for wisdom teeth extraction -people travled to him for their dental work, and he realized it could be used for surgery, contacted Morton so he could get a hold of General Surgeon in Boston (John Warren) -they met and he scheduled a demonstration to show works of nitrous oxide but the patient didn't show, someone volunteered but he yelled in pain (admitting to have no pain later) so Wells chances of using it in surgery were ruined -Morton did not give up (he was a con man), used ether in experiments and then took it into surgery, picked the brains of Charles Jackson -Jackson was a genius but a snob, Morton stole the info on how to use ether and that night invited a reporter to watch him extract a tooth -Henry Bigelow took the next step to bring Ether into surgery, contacted surgeon Warren and Morton did a demonstration the next morning -he wanted to patent it so overnight he mixed with it orange oil and acquired a new apparatus for administration that he had never used before and was 25 minutes late -it worked but his wife reported that Morton did not seem happy, maybe he knew he stole the idea or was overwhelmed -the use of anesthesia spread and new methods came about -Long got credit for experimenting with anesthesia and died the most well off of all the originals -morton (businessman) and surgeons (jackson & wells) fought over patent, acting more like thieves over stolen treasure than scientists -Wells tried to get credit as soon as Morton claimed it, but eventually he became addicted to chloroform, he ended up in jail and sobered up but realized what he had done, took chloroform, cut himself with a razorblade, and bled to death -Morton gained patent over ether anesthesia, called letheon, but even US government used it without going through him, he pushed away his family and practice to fight for his money and credit, then read an article that gave full credit to Jackson, he went to new york to get his side of the story out, but it was very hot and he dunked his head in water, he was ill and died -Jackson cosigned the patent application but claimed it was his idea, spent life battling for glory, eventually Jackson was given credit for experiments and observations and Morton for use in surgery, but neither happy with half credit, Jackson suffered a stroke and could no longer speak, and would not let anyone take care of him, was forced into an asylum for 7 years, and then died -anesthesia was a great gift to society, but it brought only pain to Jackson, Morton, and Wells, the discovery was greater than the 3 men who discovered it

Antisepsis

-Ignaz Semmelweis became a doctor in 1844 and specialized in obstetrics, he saw many women die of childbirth fever, he noticed more women died giving birth in hospitals than at home -his friend accidentally punctured his finger during an autopsy and died of the same thing, realized if a knife could carry the disease, the hands of a doctor doing an autopsy could transfer to a mom birthing a baby -he started to require doctors and students to wash their hands before entering the obstetrics ward -he did not publish his theory and another doctor at the hospital was the first to write about it, it spread to Europe but not through his writing -the idea was not accepted because it meant doctors had been inadvertently killing mothers, Semmelweis' boss Klein did not rehire him after assistant-ship -he worked in a small ob in Hungary and brought death below 1%, but faded from public, when he spoke again, he was not a scientist but bitter, calling out and blaming specific people for the puerperal fever deaths -he went mad and was taken to an asylum by his wife in Vienna, and ironically died of an infection from a cut he had received on his last patient -other history shows he may have been beaten in the asylum -after his death his idea spread, Pasteur germ theory, and at end of 19th century antiseptic techniques were an integral part of medicine -now 1/10,000 women die giving birth -may give credit to Holmes, Lister, or Pasteur, but Semmelweis was the first to have the idea

Andreas Vesalius

-Med school at 18, uni of paris, conservative instructors that followed galen and hippocrates -took knife from "barber surgeon" during dissection, finished dissection himself (only second dissection he witnessed as a student) -helped prof write book, Anatomical Institutions, prof said "a young man of great promise, witha remarkable knowledge of medicine and great dexterity in medicine" but later Vesalius said prof never did own dissections -Professor Jacques Dubois/Sylvius- first to describe muscle by insertion, strongly believed in Galen -shaped by prevailing humanism of the time which revered works of ancient philosophers & writers -Ring-leader to dissect: Raided cemeteries, esp. where executed criminals could be found -graduated from Louvain, got doctorate from Padua and began teaching anatomy and surgery there -dissection lectures became famous, published annotated anatomical charts, invited to medical school of bologna to lecture, here he learned of Galen's errors and publicly took stand against, students were excited, professors walked out -Age 28 wrote On the Fabric of the Human Body- human anatomy from dissection and physiological experiments, first accurate -Found over 200 discrepancies in Galen's work, saw that his ideas matched with apes but not humans -Taught skeleton was foundation of body, suspended skeleton above dissection table as road map) -detailed skeletal system, muscles, tendons, arteries, veins, nervous system, abdominal and reproductive organs, heart, lungs, and brain -prooved Galen's rete wrong -Provided significant detail on human brain -despite proof, could not come up w/ new, comprehensive theory of vascular system -old teacher Sylvius said he had produced nothing but "error-ridden filth" -bc of this backlash, Vesalius burned all of his works and left Padua to work for Charles V, became Europe's most respected physician and became rich -religious and medical leaders of the time spurned his work; reacted w/ rage-driven symbolic suicide (burned his works) -regretted leaving anatomy to become royal physician, didn't get credit for saving someone and decided to travel to holy land, caught in storm and died alone in island of Greece "Genius lives on, all else is mortal" knew how important his discoveries were

Hippocrates

-Medicine: Greeks, Romans, Muslims, Medeval Europe ~400 BC -1st healer to challenge prevailing belief that disease = supernatural -Said all diseases have natural causes/cures -Examining body w/ 5 senses + REASON -Created the field of medicine as we know it -"Hippocratic Corpus" : 70 loosely related medical works, common theme = conviction that health/disease = STRICTLY NATURAL PHENOMENA -PATIENT CENTERED MEDICINE -Holistic medicine -->MAKE SENSE OF ILLNESS IN CONTEXT OF PATIENT'S ENVIRONMENT/LIFESTYLE -Healing through least traumatic means possible -Humility and realism -"Help, or at least do no harm" -Physician 3 goals: 1. alleviate patient's suffering 2. reduce severity of illness 3. recognize/refrain from treating the untreatable ***Hippocrates is famous for humility, realism, holistic, patient-centered approach

Decoding the Human Genome

-Robert Sinsenheimer at U Cal Santa Cruz came up with the idea of creating an institute to map and sequence the entire human genome in 1984, but at a meeting scientists thought we did not have the technology yet to do it, so they decided on mapping only the most important parts -Charles DeLisi studied the effects of radiation on humans and organized a research program on structure of human genome in 1985, in his meeting the scientists believed it could and should be done, and even though at that rate it would take hundreds of labs and billions of dollars, they got initial funding (5.3 million) -The NIH began funding projects in 1987 as well, in 1988 they appointed James Watson the director, he spent 5% on legal and ethical implications which was very helpful in all the controversies, and by 1989 the National Center for Human Genome Research had a budget of 60 million -International effort began in 1990 and everyone agreed to make findings open to the public, goal to do it all in 15 years, by 2005 -Craig Ventor found a bunch of gene fragments but did not know the function, patented them which Watson said, "could be run by monkeys," he hated to bottom up method Ventor was using and the idea that he was patenting meaningless genes -the bottom up vs top down argument created two casualities: Watson resigned in 1992 because of his opposition to patenting which did not fit with his boss or the free enterprise of first Bush Admin, and Ventor left the NIH and joined non-profit TIGR where they poured out human ESTs by the thousands -people found these very useful, finding genes involved with colon cancer and Alzheimers -Venter proved value of gene-crunching when working with Hamilton Smith of John Hopkins, smith proposed bottom up approach to whole genome of H. influenzae (organism that causes ear infections, bronchitis) and the method became known as whole-genome shotgun sequencing, and it worked -publisher of Nature didn't like Venter but in 1995 they published "The Genome Directory' and it described 175,000 genetic sequences, first ever categorization of gene functions, and Venter opened almost all of TIGR's database to the scientific community -"The Human Genome Project could not help but notice that Venter and TIGR had already found the fingerprints of half of humanity's genes" -1998- physical and genetic maps of human chromosome, and sequenced one whole chromosome (the smallest 22) -Venter had Hunkapiller design the fastest sequencer in the world and said they would have the whole sequence in the next few years, (2001), said he would release sequences every 3 months and only patent a few hundred -Watson called him Hitler, Venters company name- Celera meaning swift, "Speed matters, Discovery can't wait." -June 26, 200, President Clinton publicly stated that the race was a tie between Venter and Collins, even though Collins turned to the machine venter was using -Celera's computer had performed "first assembly" and largest biological circulation in history top piece together the fragments -3.2 billion base pairs -vastly increased appreciation of genetic differences that make us unique -identifies 1.42 million SNPs (changes that create differences, included diseases we are susceptible to and responses to medicine), also used to identify rapists and murders because everyone is different -allowed us to sequence many organisms, and improves research on mosquitos and malaria -the original draft is still missing pieces, and it will take a long time and a lot of work to fill the gaps

cannibals kuru and mad cows: a new kind of plague

-Yabaiotu died in 1957 she lost control of her limbs emotions and ability to talk and eventually fell into a coma and died -her people have been dying like this for over half a century and they called it Kuru from the word for shivering or trembling -it often struck women and children but not men, blame sorcerers -Carleton Gajdusek Took interest in her disease and afterher death removed her brain and sent it to the NIH in Maryland -people called Carlton self-centered thick skin and inconsiderate but won't let danger physical difficulty or other people's feelings interfere with what he wants to do -Igor Klatzo studied the brain and found damage to the cerebellum which is a not at the base of the brain known to coordinate movement, something was stealthily killing neurons and found amyloid floating around neurons in children which is also seeing an elderly with Alzheimer's -Hadlow saw resemblance to brains in welcome medical museum in London there called scrapie, he told Gadjusek and they wanted to transfer the disease from a dead human brain to a primate but it took over four years -The next clue came from anthropologists Robert glass and Shirley Lindenbaum, worked with Fore, realized the women have been cannibals- only cannibals got the disease but unsure how it transferred from one person to another -chimpanzees Georgette and Daisy provided the link, Joe Gibbs working in Gajdusek NIH lab injected a tiny amount of material from kuru victims -both chimpanzees got the disease showing that it could be transferred from humans to animals and vice versa -Stanley Prusiner ventured to new guinea to work with gajdusek, discovered it did not contain DNA or RNA, protein damaging treatments reduced its strength so they thought the agent might be a protein, Prusiner are published in 1982 in the journal of science and said that it may be transferred by a protein what she called a prion -they turned it PRP when studying hamsters, and realize that there were two versions chemically identical one which could be broken down by natural enzymes another one which could not, The rug PRP turned normal PRP bad -Prusiner won the Nobel prize a 1997, it is now known that if PRP folds properly it has a normal function but if it folds improperly it may end up as infectious prion -One in 1 million can be spontaneous but if ingested it will start a chain reaction like by eating a hamburger that is infected -in 1996 people began dying from bovine spongiform encephalopathy he or BSE also known as mad cow disease, it is a new variant of CJD and it was caused by cattle -it also resulted from cannibalism by feeding meat to farm animals, The risk of spreading mad cow disease exists mama the discovery in June 2003 of a cow with BSE in Canada is the first known case in North America -The discovery of prions which are bits of infectious self replicating protein that can jump from cell to cell has created new fields of research -drugs and vaccines to protect animals from scrapie and humans from vCJD are in the works -"although it started with the study of an obscure disease and sheep and even more I'm scared to see use in humans, this research may help explain and eventually prevent such common devastating brain destroying diseases such as Alzheimer's and Parkinson's"

Wilhem Rontgen

-discovered X-rays, 1845-1923 -classmate drew a picture of a teacher and when he was caught with it he would not snitch so he was expelled, so he could not go to many European universities, tested into Zurich Poly technical School where Einstein went 4 decades later -wasn't special as a child, quiet, preferred nature to studying, was good with his hands, studied mechanical engineering but worked with physicist Kundt for 10+ years, became theoretical physicist professor -did many valuable experiments, in 1888 he showed that rotating glass plate in between two electric charges creates magnetic field (dielectric) -nothing super famous until 1895- cathode rays in glass tube and air around could make things fluoresce, he covered tube with cardboard and when he turned the lights off the glowing green traveled much further than cathode rays so he knew something else was causing it, he named them X-rays -many people before him noticed this same phenomena, but did not look into it, so he deserves a lot of credit -he was rigid, meticulous, and stubborn and worked alone in the lab -discovered the x-rays penetrated most things except metal, especially lead, and he was the first to capture pictures which included the bones of his hands while holding objects -took a picture of his wife's hand with her wedding ring, horrified her but is one of the most famous pics in medical history -he knew others could discover this so he quickly published a preliminary paper, paper published on Dec 28 1895, and became world news on Jan 5 -unlike many medical discoveries, people used it right away, papers were published (Roentgen had 2 more) and people begane experimenting with having patients drink salts and digestive organs became visible -stores and arcades had x-ray machines because people liked seeing their own bones, Thomas Edison set up a screen for it, but the negative effects were first seen in his assistant, Clarence Dally, his hands turned red and hair fell out, had to amputate one hand and some fingers, and died within a few years -Godfrey Hounsfield, a computer engineer, discovered if digitized x-rays from multiple angles were combined they could make a 3d image- CAT/CTscan- computerized transverse axial tomogrophy -Roentgen gained immediate fame, demonstrated for Kaiser Wilhelm II, first nobel prize in physics, refused laureate speech, nobility award, and donatedd money to further research at Wurzburg, and never patented X-ray or tried to make money from it -"the epitome of a meticulous experimenter, patiently toiling to measure some effect slightly more precisely than before" -he was a terrible speaker, his lectures put students to sleep and his one public speech people could not understand -"every genuine scientist follows purely ideal goals and is an idealist in the best sense of the word" -Roentgen -"how appropriate that this stubborn idealist, this diligent seeker after hidden truths, working alone in a darkened room, should have given the world an amazing tool to illuminate the innermost secrets of the human body

self and non-self

-summarizes the work of Edward Jenner (cow pox vaccine for small pox) and Louis Pasteur (cholera in chickens, anthrax, rabies) -Theories on the immune system lied in the humoral realm until the germ theory in 1870, al-Razi noticed that small pox never got the same person twice and created the theory of acquired immunity- said they lost blood and were too dry to support it again and Pasteur had a slightly modified version- first round caused depletion of nutrients -the first clue to how immunity actually worked came from Emil Behring (1854-1943)- found that blood of immunized animal generated by rod-shaped diphtheria bacillus carried a substance that protected other animals from it- called it antitoxin, injections of it sooned halved mortality rates from diphtheria which led Behring and researchers to focus on chemical immunity, soluble substances in the blood capable of destroying bacteria and toxins (key to the immune system) -Russian pathologist Ilya Metchnikoff (1845-1916) developed competing theory based on cellular immunity, working in Pasteur's lab he saw amoeba-like cells surrounding foreign particles in starfish larvae, which reminded him of similar cells in pus of wounds in humans -under the miscroscope he saw white blood cells attacking and ingesting microbes- he called these white blood cells phagocytes, two kinds: large to ingest and small to to attack, and this inspired people to research cellular immunity -then Paul Ehrlich (1845-1915) did experiments on diphtheria toxin and antitoxins and explained reaction of antigens and antibodies in terms of shape: lock and key, his theory seemed to have "won the day" -Almrith Wright (1861-1947) worked in St. Marys and was the first to try to bridge the gap between cell and serum theory, focused on opsonins, chemicals in the blood that whet the appetite of phagocytes for disease-causing bacteria -Alexander Fleming worked under Wright and spent time trying to induce opsonins in humans, but the methods were too complex and unreliable to convince anyone -researchers realized they needed to know how the body distinguished between self and non-self Peter Medawar (1915-1987) discovered that tissues grafted from one part of an animals body to another thrived, the immune system recognizes and attacks foreign tissues nut ignores tissues from self -Ray Owen found that calves did not reject tissue grafts from siblings with whom they shared common fetal blood circulation- self included siblings -The Clonal Selection Theory of Acquired Immunity- Macfarlane Burnet, David Talmage, and Joshua Lederburg- the cells of the immune system had to have enormous variety of antibodies and had to be able to differentiate into cell lines (clones) able to detect, attack, and destroy pathogens -believed that immune cells had a few antibodies and when they encountered a pathogen they could connect to they would reproduce, they did not attack self because self antibodies were suppressed in fetal development -Lederburg explained how immune system could produce enormous numbers of antibodies from small assortment of genes- suggested that key genes in immune precursor cells must mutate high rate throughout life, immune system turns this genetic instability into gold- infinite varieties of antibodies -Susuma Tonegawa validated and went beyond this theory, proved that variety stems from mutation and recombination, proved b-lymohocytes in 1981- memory cells that whose clones pour out antibodies -went to MIT to research T- lymphcytes that guard against cancer cells and cells infiltrated -decades of insight proved the immune system is complex- we know it has specificity, memory and diversity -specificity is created by cell lines, clones, or T-cells, memories are stored in b-cells in 1996 and attack on self-nonself theory led by Polly Matzinger began, she studied a little bio in high school but was bored so tried many different jobs, including being a playboy bunny,while serving drinks at U of Cal, she overheard two biologists discussing mimicry, she asked a question and they explained, and she realized research could not be boring -she was puzzled that self and nonself are set in stone before birth when microbes continuously change (ex. breast feeding produces proteins that weren't there before), she argued that self-non-self could rule things out throughout life -her question instead how do we distinguish between self and nonself was how does the immune system decide whether or not to respond -proposed Danger Model- cell death is orderly, but virus death is violent, a clear sign of danger that attracts immune cells, this signals cells to come (swollen glands), the immune system is constantly redefining what it will tolerate -her attack on the self-nonself theory has inspired more research, and there are still many unsolved mysteries within the immune system

Edwards and Steptoe and In Vitro

-the first In Vitro Fertilization was done by Robert Edwards (physiologist) and Patrick Steptoe (physician). the baby, Louise Joy Brown was born on July 25, 1978 -the drive to the discovery of "test tube babies" was of Robert Edwards (b. 1925) who's self-deprecating humor masked his superb mind and spirit -his mother encouraged his education, he was the middle child -he was separated from his family during WWII and instead of writing of loneliness he wrote of the beauty of the isolated farm he stayed at -later fought in the british army and then went to University of Bangor in 1949 for agriculture but realized it was pointless and switched to zoology, after that he went to edinburg university for graduate program in genetics -after his first year he discovered his interests in fertilization and spent hours under Alan Beatty studying mouse embryology -he only worked at night because that's when the mice were active, so when he married he decided to find a way to control when eggs ripen. HCG injections did the trick -he researched for 25 years, then convinced gynecological surgeons to give him human eggs, but once they found out he was attempting to fertilize them they stopped -while at cambridge he acquired 3 ova and decided to use his own sperm to attempt to fertilize them. others thought sperm has to be exposed to uterine fluids to fertilize, one egg was fertilized and it was "beginners luck" because he did not see it again for several years -in 1966 he met Edward Steptoe, a a London gynecologist, and he had pioneered the use of laparoscopic surgery, making IVF a more practical option -Edwards decided he would make a great team with Steptoe when he heard him blast a doctor at a meeting who said laparoscopic surgery was worthless -Edwards was 165 miles from Steptoe, but they built a lab and worked together, he made the trip over 750 times -the men had very different backgrounds: Steptoe had a large happy family, but both had a strong relationship with their mothers, when they reached obstacles, steptoe quoted his mother "obstacles are opportunities in disguise" -Steptoe spent 2 years as a prisoner of war in italy during WWII then he moved to oldham with his wife from london where he produced many research papers on gynecological laparoscopy -he had access to many human eggs so their work progressed and by 1968 they fertilized human eggs and saw them develop through several cell divisions -in 1969 they receive backlash for their research, it was "morally wrong" but edwards description (comparing what the cells he saw under the microscope to the stars in the sky, equally amazing) you could tell how they felt -childless women were almost too eager to give themselves over -they found the dose and sequence of hormones to stimulate ovaries to produce ripe eggs, the timing to laparoscopicly get the ripe eggs, improved culture medium from Barry Bavister, they were able to nurture eggs to 8 cell stage and implant them into womb -the first attempt failed, and so did many after it -many people again argued that their work was unethical, including James Watson, but they received funding and a clinic from local ethical committee and health authority, so they set up a lab and operating room -in 1977 steptoe was about to retire, and as a last ditch effort they decided to get an egg naturally instead of forcing them out on Lesley Brown. they waited and she became pregnant and it progressed satisfactorily -steptoe put her in the hospital at 8 months because of high blood pressure, and they were surrounded by reporters, one even phoned in a bomb threat in hopes of the mom being taken outside -delivered the baby by c section on July 25th, 1978 and he had to sneak his surgical team past press one by one, and Mrs Brown was escorted to the operating room by dozens of police -the baby was born at 11:47, pink and furious, and externally perfect and beautiful -the catholic church condemned IVF and there was a lot of moral outrage, but Brown had her second child via IVF. just before Louise Joys 10th birthday, Steptoe died at age 74 -since then the number of IVF babies has skyrocketed but the procedure remains complicated, costly, and risky -women now have to go through cycles of hormonal priming, egg harvesting, and implantation and fewer than 1/3 become pregnant -to increase chances, doctors implant multiple embryos, which increases likelihood of multiple births -fertility research at Stanford, Barry Behr, warns against multiple babies because it creates more risk, and encourages use of new medium that allows embryo to grow longer (5days) which means they have a higher chance of surviving, doubles the chance of conception and reduced risk of multiple births -Edwards predicted the use of embryonic stem cells to cure disease and replace organs -competing teams from University of Wisconsin and Johns Hopkins announced isolation and culture of primordial human still cells, embryonic cells capable of growing into human tissue in 1998 -"For better or worse, the child has been born. How it will grow remains in our hands." meaning if these discoveries are used for good or bad is still unknown

Edward Jenner

-was given smallpox so he could hopefully survive and never deal with it again at a young age, it worked -inoculation was common, 1/20 developed full disease and it often caused a contagion -historical references to smallpox from time of Rameses V (1157 BC); often killed 9/10 people -often determined course of history across numerous continents and societies -Major american smallpox epidemic: 1775-1782 (note proximity to 1776 -survived inoculation at age 7 by his brother, went on to be known as father of immunology -left home at 13 to apprentice w/ local surgeon- apothecary, then study w/ famous surgeon, comparative anatomist, naturalist, John Hunter -chinese determined if a person survived this, they did not get it again: established a method of innoculation -Mary Wortly Montagu survived it as a child, wife of ambassador of constantinople, brought inoculation process back to England -he went to his home town to settle down and become a doctor, but Hunter always nagged him to do research -Hunter (mentor) pushed him in late 1790s to study using case studies the processes of cow pox, small pox, how to successfully inoculate -drafted paper to Royal Society, rejected, he had 13 case studies and only one experiment that inoculation with cowpox could prevent smallpox, so it wasn't enough -later he did more experiments and many worked, but one child died and he was criticized for covering up the death -his paper on this Variolae Vaccinae is famous and one of first on vaccines -William Woodville began vaccinating people in hospital for smallpox, but found the cowpox was infested with smallpox so many got sick, when he vaccinated in private office, itworked -Fiercest criticisms of vaccination from clergy as against God's will & use of animal material in humans = abomination -Thomas Malthus said vaccines were wrong because disease limited the number of poor people -how did society control progression/use of this info how long does it take for vaccination to be seen as acceptable?--> UK accepts smallpox vaccination by 1853---> pasteur and koch need another 60yrs -175 yrs before WHO brought to the World *** Public in Jefferson's time did not want to acknowledge that ppl & animals may share similar diseases, how likely are public in our time to recognize many other aspects of health and healing are not medicines and surgeries?? (I.E value of environment, music, OUR MINDS)

Johann Weyer

1515-1588 -Faith dictated from on high replaced reason & observation, witch hunt began mostly on poor women, thought crop failure, hunger, and plague to be work of Satan through witches -Middle Ages: Europe lost touch w/ science, medicine, rationalism of ancient Greece & Rome -Medicine became hodgepodge of potentially useful remedies w/ bizarre compounds, chants, amulets, prayers -in europe, witch hunt compared to Holocaust, leaders followed book Malleus Maleficarum which is cruel and misogynistic, "perhaps most terrifying ever written", explained how to identify and kill witches, its values began to dominate, targeted women bc they were considered weak -Lone voice in oppositions against witch hunts, instead saw them as vulnerable, mentally ill -Wrote "On Witchcraft"- one of few to publicly state that demonic tales were meaningless -first to argue "mental illness" and natural phenomenon as causes. showed just sick and desperate women who needed treatment not torture--> women defined as inferior and impure by nature: natural and willing tools of the devil, stories were products of dementia, mania, depression or misuse of drugs -for this stand and pains he took to study witchcraft he is often seen as the founder of modern psychiatry -his book had some effect, but he was still persecuted, Jean Bodin lead an attack on him, accused him of being a wizard -He however was also accused of being in leagues w/ witches & died in exile b/c Duke Wilhelm (his protector) suffered a stroke and became demented and the Duke's son also became psychotic (witchcraft had spread) -hight of witch hunts were 1600s (century after Johann) but continued almost to 1800s "Love your fellow beings, destroy errors, and fight for the truth without any cruelty" -Johann "Know with what pain truth is obtained and with what difficulties one guards one's self against errors" -Johann "society has not freed itself from the potential to descend into madness, especially when fanatical ideologies take control of the state" -Adler

William Harvey

1578-1657 -conservative thinker, painstaking observer, slow to hazard a conclusion -Loyal to Galen & Aristotle's teachings; took 12 years to publish findings; not in his nature to upset established order and feared controversy -went to a good school and then college where he was elected by his peers, married a daughter of a physician, led a normal life -started w/ animals, heartbeat = too fast, switched to studying cold-blooded animals; eventually traced work to arm learned how blood flow worked & resembled a circle -wanted to understand the connection between beat of heart and pulse in veins -understood the relaxing and contracting of the heart muscle and that the pulse in the arteries was a result -would block off arteries or veins to observe the effect which allowed him to trace the flow of blood perfectly (block vena cava and heart empties, block aorta heart swells) -Put numbers to amount of blood expelled by the heart, heart pumped more out in an hour than body weight, so it had to be recycled -could not see capillaries so stuck with the pore theory for transport between arteries and veins -1628, published de Motu Cordis (mvmnt of the heart), most ppl began to accept his work after his death -biggest protestor was Riolan, because his ideas upset all of Galenic medicine -humors and treatment through purging and bleeding continued for over a century -Inspired scientists/physicians after him to use experimentation to ask HOW things worked (more so than WHY) -unlocked the heart and the importance of observation and experimentation -"All we know is still infinitely less than all that still remains unknown"

Louis Pasteur

1822-1895 -"the most perfect man who has ever entered the kingdom of science" -wasn't the best in school at a young age but good at art, began studying crystals which lead to fermentation, microbes cause fermentation and decay, microbes in sheep and silkworms, and eventually disease in humans -founded stereochemistry by observing right or left crystals -a friend asked why sometimes his beet juice did not ferment, Pasteur discovered when fermented only one organism (yeasts) were present, but when bad there were many organisms like bacteria present -Pasteurization is heating the liquid just enough that it kills the organisms -his daughters death by Typhoid fever motivated him to find the cause of infectious disease -silkworm disease spread, he studied and verified microbes as cause, then proved it later -he had a stroke and it stopped him from work for months, other people had mentioned germ theory before, but the idea of humors still prevailed -voted onto french academy of medicine and argued for Lister's hand washing and other ideas, argued so strongly that he was challenged to a duel -began researching Anthrax competing with Robert Koch who was known for research on bacteria and anthrax -proved germ theory with anthrax disease by culturing it 12 times- original chemical composition gone but still infected animals injected, meaning living things had to be the cause -advance came with chicken cholera, his culture was left to sit and no longer caused infection, then infected with live virus the chickens survived- first advance on vaccination since Jenner's smallpox -he saw what other's missed and discovered things by accident, "in the field of observation, chance favors the prepared mind" -created vaccine for anthrax and was asked to test it publicly on a farm, all of vaccinated animals survived while unvaccinated died -developed a way to create immunity against rabies, worked a long time on animals, then asked to intervene on two patients with bites, and they both survived, in 1888 Pasteur Institute was opened and known for not only curing rabies but for research on many things -died after 2 more strokes, "before he died, he had fulfilled his own call to battle- he had transformed the world through his discoveries"

Sigmund Freud

1856-1939 -forced the world to recognize the reality and importance of the unconscious mind -he was his mothers favorite kid so he felt destined to do something great -people used to blame mothers for the childrens neuroticism -did not have the strong father figure he needed, his dad was very passive and once told Sigmund he would never amount to anything, so he always sought approval from him -incredible student, started school a year early and finished top of his class last 6 of 8 years, his sister's piano was banished from the house so he could focus, photographic memory and knew many languages -started in medicine but liked the lab better than physician work, studied under physiologist Brucke who wanted to rid bio of all religion and believed all life processes could be explained -Freud came close to explaining nerve cells but never followed through -fell in love with Martha Bernays and knew he could not support her as a researcher, married in 1886 after many years of chasing after her, married for 51 years and had 6 kids -began clinical work in Vienna hospital in 82 to support a marriage, focused on neurology and psychiatry -experimented with cocaine and published on it's pain relief and morphine addiction benefits, but later discovered it was also addictive -went to Paris to study "nervous patients" under Charcot, who was one of first to prove mental illness was a medical problem -opened his own practice in Vienna and many did not believe him, but Breuer did and they published on Hysteria together in 1895 -in these years he developed core of psychoanalytic theory of the human mind, and was convinced that there was a cure to mental disordered that lurked behind the conscious mind -began with hypnosis and then suggestion, but neither produced results -he was a keen observer, began using "free association" asking patients to say the first thing that comes to mind and it often revealed something -believed that conscious awareness is only a fraction of what goes on in the mind -hypothesized 3 parts of the mind 1. id- sources of instinct and driven to seek pleasure in action or fantasy 2. ego- balance id with restrictions of reality 3. superego- monitoring and judging ego like an omniscient parent -said that main drive was sexual, there is no "age of innocence," sexual feeling begin in infancy -breastfeeding followed by series of steps struggling to meet needs, for boys the Oedipus conflict (attached to mother so sees father as a rival, then out of fear becomes like and attaches to father and later in life the female attachment is shifted to another woman) -published Interpretation of Dreams in 1899, then The Psychopathology of Everyday Life, ordinary events like jokes, slips of the tongue, and misplacing objects contain information, revealing unconscious wishes -the battle between id, ego, and superego show themselves in psychiatric disorders, Freudian slips -published The Three Essays on The Theory of Sexuality, normal and abnormal sexual development (1905) -oral, anal, phallic, and genital phases, libido can be attached to objects or people, explained abnormal sexuality in transition through phases -1923 diagnosed with cancer from smoking, underwent over 30 procedures but refused pain medication to keep his mental acuity, forced out of Vienna when taken by the Nazis, died in England while working on Outline of Psychoanalysis in 1939 -no one has created such scientific impact except Darwin -later attacked in 1984 for not pursuing the idea that sexual abuse of children caused problems because it was so controversial, claiming that memories were fantasies, so Masson argued all of ideas were based on a false premise -key ideas: motivated by unconscious sexual and aggressive drives, shaped by early experiences, torn by inner conflicts, defend ego from unpalpable truths, and can be helped by psychotherapy, are still important today -"we are no more aware of what goes on in our brains than moviegoers are aware of what goes into producing a movie"

Herophilus

330-260 BC Alexandria -Father of Anatomy -Primarily interested in describing WHAT HE SAW -Dissected and studied human body from head to toe -Distinguished btwn 2 complementary parts of brain -Said human consciousness in brain, not heart (different from Aristotle) - 1st to figure out that nerves create movement (not arteries) -differentiated between arteries and veins- arteries thicker -describes the reproductive systems, especially female, contributing to obstetrics -named the duodenum, retina, and the sinuses in the brain are named after him- torcular Herophili -1st to link pulse to heartbeat, first to time pulse (thought arteries contracted on their own in response to heartbeat) -Learned medicine via Hippocratic influence- taught by Praxagoras of Cos follower of Hippocratic school -Discovered/described prostate, spermatic duct, fallopian tubes, ovaries, duodenum, female repro system

Abu Bakr al-Razi

~865-925 -"all authorities and accepted knowledge need to be questioned," "each generation has the opportunity to move science forward through new observations and experiments" -1st to bring up questioning authority, not having blind belief in absolute truths of religion -Wrote all men are created equal -might have injured his eye in youth --> visited doctors and became interested in medicine -provided excellent details of disease which helped (later) finding a cure -1st to classify animal, vegetable, mineral -wrote over 200 books, 50 on medicine -director of a hospital for the rich in Baghdad but also had a clinic for the common people -differentiated between measles and smallpox -wrote book for the common man "he who has no physician to attend him" -wasn't afraid to say that Galen and others before him were wrong if his observations and experiments proved it -father of pediatrics & opthalmology -wrote extensive textbook of medicine that combined everything they knew at the time, Comprehensive Book on Medicine - on European medicine Charles Singer said, "anatomy and physiology had perished.. prognosis was reduced to rule of thumb... medicine deteriorated into a collection of formulae punctuated by incantations" -in 1279 a Jewish physician translated the medicine book into Latin, the ninth book was used as a medical text in schools until 17th century -wrote a book on smallpox, incredibly detailed and based on his experience working with patients, including what seasons it is most common and ways to prevent it (no cure), also listed the symptoms accurately -he was anti-religious which enraged a lot of people -he died "blind, battered, and embittered," a surgeon offered to remove his cataracts and he said "I have seen enough of the world and have no desire to see it further" -"his belief in freedom of thought and inquiry, in the progress of scientific knowledge and in the values and capabilities of ordinary people would be briliantly vindicated"

Galen of Pergamon

~AD 130 -200 -father was a mathematician and his mentor, mother was shrew and mean, he got characteristics from both -physician to the gladiators --> opportunity to deepen his understanding of functions of nerves & tendons -Brilliant diagnostician & gifted healer, moved to Rome and showed off his skills--->also a showman, not above using trickery -sharp tongue, boastful -called back to Rome by marcus aurelius to tend to the heir of the throne, Commodus -large portion of his 700 works burned in fire, but half of greek medicine words belong to him, and 5/6 non-hippocratic are his -Many of his great advances made at dissection table --> human dissection was forbidden, dissected animals (pigs) -first to sever spinal cord of living animals at different levels- used apes because he thought they were similar to humans -function of the diaphragm and chest muscles and breathing and traced control of machineray of breathing through nerves to the brain -First to prove arteries normally filled w/ blood -proved pulse originated in heart, blood flows outward from heart thru arteries -exposed an animals heart and put a tube in left ventricle, with each pump, blood squirted out, not pneuma -still believed pneuma was incorporated through pores in the ventricles -created a system: arteries carry blood charged with pneuma and intrinsic heat, veins filled with blood and vegetative pneuma, and nerves carried psychic pneuma pumped out by brain to muscles and sense organs, liver converted digested food to blood and sent it to heart and created vegetative pneuma -three categories of disease: specific organs, tissues, and humors -believed in a Supreme Intellect who fashioned the human body perfectly -established himself as "The Prince of Physicians" -"groundbreaking studies and overarching systems paralyzed medical progress for nearly 1500 years -his false ideas were maintained until the renaissance when people began using a scientific foundation for medicine