lecture slides 19-28
Linus Pauling
provided the first description of a genetic disease - sickle cell anemia (linking a disease to a single gene). He contributed to the stigma surrounding carriers of genetic diseases by suggesting every person with the sickle cell gene be marked with a tattoo.
Otzi the Iceman
an extremely well-preserved glacier mummy from the Copper Age. He was found with a pouch of birch fungus (possible medicinal properties) and with tattoos over his arthritic joints
Asclepius
the Greek God of Medicine, who oversees disease and health. ‘Healing’ temples were built dedicated to him and priests there provided advice on how to get better
Who was Hippocrates?
A Greek physician who studied and wrote about many diseases
Who was Galen?
a prominent Roman physician to gladiators. He conducted dissections and vivisections of animals, basing his human anatomical drawings on the anatomy of monkeys. His theories dominated and influenced Western medical science for well over a millennium.
Who was Andreas Vesalius?
Belgian anatomist who debunked Galen’s ‘Four Humors.’ The printing press was created during his time, which helped spread his translation of Galen’s Greek texts and his critique of Galen’s idea.
Who was Crawford Long?
American surgeon who developed an anesthetic (induces a reversible loss of consciousness) and tested it on slaves
Who was Robert Liston?
the “fastest knife in the West End” (during pre-anesthesia era); he amputated a leg in 2.5 minutes (patient died of gangrene) and accidentally amputated the fingers of his assistant (who also died of gangrene)
Who was Ignaz Semmelweis?
Hungarian physician who studied and wrote about puerperal (childbed) fever, a bacterial infection of the female reproductive tract acquired after birth or miscarriage. Semmelweis noticed that ‘cadaverous poisoning’ was on the rise in a hospital that housed cadavers in one wing and delivered babies in another, and doctors were not washing their hands going from one to the other. He suggested putting hand-washing stations in between but many doctors refused and could not believe their hands could transmit disease (‘Semmelweis reflex’).
What did Warren and Marshall discover?
They discovered H. pylori in 1984 and linked it as a cause of stomach ulcers. Marshall drank a beaker of H. pylori and developed gastritis, which he later cured himself of with antibiotics. They won the Nobel Prize in Medicine in 2005.
Jonas Salk
developed the first successful polio vaccine (with HeLa cells)
John Enders
isolated the virus that causes measles and developed a live-virus measles vaccine
Malone Mukwende
medical student who co-authored Mind the Gap: a clinical handbook of signs and symptoms in black and Brown Skin
Andrew Wakefield
published a study claiming that the MMR vaccine was linked to autism. It was later revealed that he fixed data and his medical license was revoked.
Joseph Lister
founder of antiseptic surgery. He sprayed phenol (carbolic acid) around the surgery arena and cleaned tools with it. Listerine mouthwash was named after him.
Marcello Malpighi
one of the first biologists to make use of the newly invented microscope and is widely regarded as one of the founders of microscopic anatomy.
Selman Waksman
awarded a Nobel Prize for his studies that led to the discovery of streptomycin (an antibiotic). He was able to cure guinea pigs inoculated with TB.
Alexander Fleming
unintentionally discovered penicillin (accidentally grew it on a petri dish). He did not test it on guinea pigs which was unknowingly good as penicillin is toxic to guinea pigs and the antibiotic would have been ruled unsafe.
Henrietta Lacks
A woman whose cells, taken from a cervical-cancer biopsy, became the source of the HeLa cell line which is the first immortalized human cell line. Normal cells die after dividing a certain number of times, but Henrietta’s cells can divide infinitely due to a lack of growth checks.
Jesse Gelsinger
man who had a mild version of ornithine transcarbamylase deficiency and volunteered for clinical trials of an OTCD gene therapy. He was injected with an adenovirus carrying corrected genes, but it triggered a severe immune response in his body and he died of liver failure.
David Vetter
‘the boy in the plastic bubble’: a young child with a very weak immune system and had to stay completed isolated. He died from an infection after being le tout of his ‘plastic bubble’ for a short time.
Mary Mallon (AKA Typhoid Mary)
Mary was a carrier of the typhoid bacteria but did not present any symptoms. She worked as a cook and infected a lot of people, and was eventually forced into isolation.
stigma from disease
a stigmatized individual is one who is not accepted by their peers, “one who should be avoided.”
What is public stigma?
negative public perception of those infected with a disease
What is self-stigma?
avoidance of testing or going out for fear of public perception
what is label-stigma?
When there is no evidence an individual is infected and/or contagious but they are avoided or labeled as such
What are the 4 types of disease-avoidance?
Visible/contagious: physical symptoms of contagious disease (sneezing, runny nose, rash)
Visible/non-contagious: visible medical conditions that are not contagious (down syndrome, nevus flammeus)
label/contagious: a disease with no visible symptoms, but someone assumes an individual has it (from stereotypes, for example)
label/non-contagious: non-contagious individuals being labeled as contagious
What is emotional disease-avoidance?
when visible disease cues directly activate feelings of disgust or contamination
What is cognitive disease-avoidance?
when disease labels bring to mind diseases cues, indirectly activating feelings of disgust and contamination
What were some consequences from stigma surrounding Ebola?
Survivors were avoided upon return to their homes
Children who lost parents and were living in orphanages were not claimed by their relatives for fear of being infected
People avoided hospitals or didn’t receive treatment
What was the primary cause of disease in pre-agricultural times?
malnutrition from a diet of mostly grains and very little to no meat. Common associated diseases were iron-deficiency anemia and cavities (from eating high sugar plants)
what was a ‘Shaman‘?
a prehistoric doctor that acted as an intermediary between the natural and spiritual world. They used medicinal herbs, clay (setting a broken bone in a clay cast), and earth (sometimes eating dirt, which contained some helpful bacteria), and performed trepanation (making a holed in the skull to ‘let the bad spirit out’).
examples of human diseases that originated from zoonosis
measles, TB, smallpox, influenza, and whooping cough
what did Priest Physicians in ancient Egypt do?
they were mediators between patients and Sekhmet (warrior goddess, bringer of disease, and provider of cures), who also practiced mummification which helped them gain an understanding of human anatomy. They wrote about ailments, medical treatments/cures, and anatomical observations on papyrus (which they invented).
what ‘Rules of Hygiene’ did Hebrew doctors reccommend?
precautions around wounds, skin, and discharge; waste disposal; isolation; burial precautions; and food/drinking water safety
Where does this medical symbol (the Rod of Asclepius) come from?
a statue of Asclepius holding a stick with a snake wrapped around it
and/or
a parasitic worm infection prevalent in ancient times, which required doctors to pull out the worm in one piece by gently rolling it around a stick
what was the Miasma theory?
a medical theory that inhalation of the nasty smell from organic matter caused diseases such as the Black Death
What are crowd diseases?
infectious diseases that spread rapidly in crowds or areas of high social contact
What is the Hippocratic Oath?
the ‘ideal conduct for the physician,’ written by Hippocrates. The modern version not entirely the same as the original, but the main ideas of doing no harm and compassion for patients persist.
What is the idea behind the Hippocratic School of Medicine?
the body has the natural ability to heal and balance itself. Bodily health is based on the balance of the four ‘humors’: blood, yellow bile, phlegm, and black bile. If one of the humors is out of balance, it will affect your body and emotions.
What were barber-surgeons?
after “bloodletting” was declared sacrilegious and priests were barred from performing it, barbers started offering a ‘bloodletting’ service during haircuts. Barbers eventually began providing surgery and dental work and in the 13th century the first school for barbers in the practice of surgery was created. This school became the model for schools of surgery in the Middle Ages.
What types of anesthetics are there?
Nitrous oxide, ether, and chloroform
What are some notable 20th century medical inventions?
Blood transfusion, plastic surgery, organ transplant, in vitro fertilization, and incubators for pre-term babies
helicobacter pylori
a bacteria that lives in the mucosal layer lining the inner stomach and inflamed the epithelial cells (gastritis), which can cause ulcers and stomach cancer
what is the ‘disappearing microbiota’ hypothesis?
bacteria that have the potential to harm us but may also play an important role in our health and decreasing due to use of antibiotics. Some scientists hypothesize that the loss of H. pylori from the human microbiota underlies some of the diseases that are becoming more prevalent.
what is the ‘hygiene hypothesis’?
Asthma and other auto-immune diseases are on the rise because the human immune system doesn’t face enough microbes in today’s cleaner environment and is picking fights with the body’s own system instead.
Development of a proper immune response is thought to depend on exposure to germs, dirt, certain types of infection, and environmental factors. Lack of early childhood exposure to infectious agents may increase susceptibility and stunt maturation of the immune system.
poliomyelitis (polio)
a viral infection, acquired though fecal-oral transmission, that causes loss of mobility and paralysis. Polio was eradicated in the Americas by 1994 thanks to the OPV (Oral Polio Vaccine).
What is speculated to have facilitated the 20th century epidemic of polio?
too much sanitation; prior to the 20th century, poor sanitation resulted in regular exposure of infants to low levels of the polio virus. When sanitation practices increased in the 20th century infant exposure to the virus was reduced, so when children were exposed at a later age they lacked immunity and infections tended to be more severe.
OPV (Oral Polio Vaccine) vs. IPV (Inactivated Polio Vaccine)
OPV: live and weakened poliovirus strains, oral administration, $0.15 per dose, prevents person-to-person spread. Over 20 million doses given to nearly 3 billion children worldwide in the last 10 years, reducing disesae prevalence by >99%. Administration has ceased because, on extremely rare occasions, the OPV can cause infection with cVDPV (Circulating Vaccine-derived Poliovirus).
IPV: inactivated poliovirus strains, injection, $1 per dose, cannot stop spread of the virus
What is the development process for flu vaccines?
Government health agencies send virus strains to vaccine manufacturers, then the virus is injected into fertilized hen eggs where it incubates and replicates until it loses the ability to infect humans
Why do we need a flu vaccine every year?
viruses undergo continuous antigenic change, meaning the genetic material and thus the surface proteins are constantly changing, so a strain from a year prior may be too different from one circulating in the current year for our body to recognize it. Because of this, eradication of the flu is unlikely to ever happen.
What are the HA (hemagglutinin) and NA (neuraminidase) proteins on influenza type A?
HA allows the influenza virus to bind and enter cells, and NA allows for exit and spread. There are 18 different HA subtypes (H1-H18) and 11 different NA subtypes (N1-N11).
Antigenic drift
an accumulation of mutations in a virus over time, which alters its composition of proteins and may make it unrecognizable to our immune system
antigenic shift
‘reassortment’ of RNA in influenza type A viruses which occurs when an intermediate host gets infected by two different types of influenza type A (essentially an influenza hybrid).
The H1N1 virus shows evidence of viral reassortment (contains avian, human, and swine flu RNA segments)
can coronaviruses re-assort like flu viruses do?
no, because coronaviruses do not have segmented genomes
antibody-mediated immunity
immunity conferred from the production of antibodies by plasma B cells, which are freely floating in the bloodstream.
next generation vaccines
mRNA injections that code for spike proteins of a virus, which the body replicates as if it’s the body’s own RNA. This creates a spike protein, which is sent out of the cell so that the immune system responds and creates an antibody for it.
measles
a highly contagious, viral respiratory infection spread through airborne particles. Measles can damage the immune system (‘immune amnesia’), has an R-nought of 12-18, and requires herd immunity of 92-94%.
what type of vaccine is the SARS-CoV-2 vaccine?
a live, attenuated virus
what type of vaccine is the hepatitis B vaccine?
protein subunit
what type of vaccine is the flu vaccine?
a whole, inactivated virus
vaccine exemptions
many states allow religious or philosophical exemptions for childhood vaccines (CA only allows medical exemptions). The American Medical Association is strongly opposed to any type of exemptions that isn’t medical.
Anti-Covid-Vaccine protest themes
support for individual freedom/rights, opposition to government control, anti-science reasoning/misinformation, and loss of trust in science
parasites
Organisms that live in or on another living organism (its host) and benefits by deriving nutrients from them. They are the most common life form on Earth (every known species has at least one unique parasite).
bacteriophages
viruses that infect and replicate only in bacterial cells (they are very specific to the species of bacteria they can infect)
saprobes
organisms that take nutrients from dead or decomposing organisms
extinction vs accommodation of aggressive parasites
Parasites have evolved to get access to a host’s resources before they die, providing an advantage over saprobes. Now parasites must compete with other parasites to achieve more rapid exploitation of live hosts.
Aggressive parasitism causes earlier death of the host which results in extinction, so selection favors attenuated parasites.
vestigial organs/structures
organs, body structures, or genes that are hypothesized to have been helpful at a time but no longer serve any purpose (“bislagiatt”)
heterozygote advantage (PKU, sickle cell anemia, cystic fibrosis)
when a person who carries only one diseased allele has greater fitness than a person with two normal alleles. For example, African people who are heterozygous for sickle cell disease have the ability to withstand malaria
why have life-threatening diseases such as Huntington’s disease not been eradicated from the human gene pool?
because certain diseases provide an evolutionary advantage for heterozygotes (heterozygous sickle cell disease confers protection from malaria) or symptoms don’t develop until the individual is past reproductive age (Huntington’s).
Faustian bargain (hypothesis about Huntington’s)
a hypothesis that having a longer chain of CAGs on the huntingtin gene allowed our brains to grow larger, but now we have too many which causes Huntington’s disease.
disease mongering (ex: Listerine)
the action of deliberately making a common symptom or normal behavior sound as if it’s a sign of a serious disease/issue that must be treated. Tactics include disease-awareness campaigns, re-definition of diseases, direct-to-consumer advertising, and funding for disease advocacy groups.
The company that created Listerine mouth wash originally sold it as a floor cleaner, but the market was too small so they began an aggressive marketing campaign based on exploiting human insecurities of bad breath by claiming it is an illness (halitosis).
role of the FDA in drug approval and advertisements
the FDA does not review all drug ads before they are released
guinea pigs
the term “guinea pigs” is a metaphor for a subject of scientific experimentation because these animals were very commonly used in early experiments (and are still used in research today, though not as commonly as mice and rats)
streptomycin
the first antibiotic discovered. It is not as widely used today due to side effects but it is used as part of a multi-drug treatment for TB.
penicillin
an antibiotic that was accidentally discovered by Alexander Fleming and has since been used to treat several different bacterial infections.
testing subjects for blood transfusion
during the development of blood transfusions, the optimum concentrations of citrate for the preservation of red blood cells was unknown so dogs are rabbits were used to find the optimum concentration.
tamoxifen
an estrogen modulator used to treat or prevent hormone-receptor positive breast cancer
human guinea pigs
Throughout history humans have been used as test subjects, sometimes without their consent or knowledge, and other times as volunteers.
Joseph Mengele used humans in Nazi concentration camps for medico-military research, such as pushing the human body to extremes like freezing temperatures, and for racially motivated experiments (such as forced sterilization).
Healthy individuals can volunteer for Phase I clinical trials to test safety or side effects of a potential drug, and diseased individuals can volunteer as an “altruistic trial” to test new treatments for their disease.
Tuskegee Syphilis study
a clinical study by the US Public Health Service to study the natural progression of untreated Syphilis in African American men. Part way through the study, penicillin was found to effectively treat Syphilis but the subjects were not told or given the treatment.
This led to changes in US law and regulation on protection of clinical study participants. Unfortunately it severely affected African American mens’ trust in medicine and cause an increased mortality rate (black males disproportionally died of Covid-19 in several states)
informed consent
the process in which potential participants of medical research or clinical trials are given an explanation of the purpose of the study, what their role will be, and the potential risks and benefits.
Willowbrook State School
An institution for children with intellectual disabilities. The measles vaccine was tested on over 1500 children at this school.
adenoviruses
a group of viruses that typically cause mild respiratory infections.
Adenoviruses are the most commonly used vector for gene therapies.
placebo effect
when a persons physical or mental health appears to improve after taking a placebo treatment
quarantine
isolation of infected or immunocompromised individuals
spread of Bacterium Yersinia through trading routes and war
Trade routes to Central Asia brought outsiders who did not follow local customs to avoid hunting flea-infected marmots. As infected fur was traded, the fleas eventually jumped to black rats, which facilitated the rapid spread of the Black Plague throughout Europe (largely due to close contact between humans and black rats, mostly in homes).
Black Death in Europe (1346-1351)
Infected black rats transmitted the virus to humans, however humans were a dead end (no human-to-human spread, due to the virus being highly virulent). 25-30 million people in Europe died and it took over 150 years for the population to recover. The plague ended because brown rats (less susceptible tot he plague and preferred living in sewers) displaced black rats.
cytokine storm
a systemic inflammatory syndrome involving immune-cell hyper-activation and elevated levels of circulating cytokine cells that can be triggered by various therapies, pathogens, and autoimmune conditions.
antibiotics: definition, modes of action, and mechanisms of bacterial resistance
Antibiotics are a compound or substance that kills or slows down the growth of microorganisms (bacteria or fungi).
Some bacteria have the enzyme penicillinase, which inactivates penicillin. Bacterial resistance is accelerated by horizontal gene transfer (sharing of genes between bacteria) and the spread of resistant strains among patients in hospitals (mostly via healthcare staff).
superbugs
bacteria that have become very resistant to a wide range of antibiotics
use of antibiotics in factory farming
antibiotics are widely added to the feed of livestock to keep the animals healthy in situations that have high risk of sickness (overcrowding, stress, unsanitary conditions) and because antibiotics promote faster growth (in poultry and pigs).
soil as a source of antibiotic-producing microbes
soil is the world’s greatest source of microbe biodiversity, so scientists have began searching soil for antibiotic-producing microorganisms
sickle-cell disease
a heritable gene mutation that causes the blood disorder Sickle-Cell Anemia. Individuals with this disorder have a mutation in the hemoglobin gene, which causes sickle-shaped red blood cells that are less efficient at carrying oxygen and tend to stick together and clog vessels.
dracunculiasis (Guinea worm disease)
a parasitic worm infection spread through contaminated water. The traditional treatment is to slowly pull the worm out of a wound over a period of hours to weeks by winding it around a stick.
flu
An acute respiratory infection caused by influenza viruses. Influenza viruses possess an animal reservoir including humans, horses, cats, birds, pigs, whales, and seals.
H1N1 and H5N1 influenza
H1N1: Swine Flu, which is a type of influenza A virus that shows evidence of viral reassortment (contains genes from pigs, birds, and human strains). It is highly contagious and deaths are not rare (2009 H1N1 outbreak)
H5N1: Avian influenza A, which has killed millions of poultry and is highly fatal to humans (60% case fatality in a 2005 outbreak in humans)
type I diabetes (adaptation)
hypothesis that diabetes evolved as an adaptation to the sudden onset of the last ice age which protected individuals from freezing
appendicitis
inflammation of the appendix (a vestigial organ that is believed to have once served as a fermentation chamber for intestinal bacteria which helped digest plant materials)
Restless Leg Syndrome
An urge to move the legs due to an unpleasant feeling, and worsening of symptoms when at rest which can interfere with sleep.
Requip (a drug for Parkinson’s patients) was approved by the FDA for RLS patients in 2005 after an “awareness” disease mongering campaign by the company owning Requip.
osteoporoisis
more of a risk factor than a disease (the link between bone density and fractures is the subject of controversy), but companies use disease mongering to sell drugs for osteoporosis