week 2 Flashcards
Blood in Culture
- Earliest use and reference?
– One example: goddess Lamashtu (5000 B.C. Mesopotamian culture) who drank
blood of humans - Legends and origin stories as explanations for features of earth and
humans
– One example: upon death, god P’an ku/Pangu blood becomes the Earth’s rivers
(Chinese mythology) - Rituals involving
– Cleansing and purification
– Sacrifice
– Rite of passage
– Bonding
– Symbolic oath
– Conferring life, knowledge, courage, absolution, salvation, membership, and
more
Egyptian history
– Egyptian writing shows cases of blood
letting (phlebotomy)
– Imhotep was a healer to the pharaohs and
his descriptions of conditions were detailed,
almost clinical (2600BC)
* Imhotep was also an architect among other things and
was later deified
Greek history
– God Aesclepius was the healer and may have been copied off of
Imhotep
– Hippocrates (he of the medical oath) formulated the idea of the 4
humors, which was later popularized by the influential physician Galen
– Herophilus studying in Egypt described the pulse and the alternating
systole/diastole cycle of the heartbeat. Also noted differences among
vessels.
– Erasistratus proposed the flow between veins and heart and blood
production at liver
– Galen described blood flow in arteries, and even hinted at a role for
the spleen in blood production, calling it a “plenum mysterii organon”,
“an organ filled with mystery” (200AD)
– The 4 humors idea persists as a dominant explanation of health
– Dionysian or Bacchanalia tradition: wine symbolized blood and the sap
of life
Middle Ages
– Central heart pump and pulmonary circuit is described by Ibn al-Nafis
of Cairo (1200s, but forgotten!)
– Andreas Vesalius’ careful dissections and descriptions define the
circulatory system in high detail (1500s)
– Hieronymus Fabricius draws the valves present in veins (1600s)
– William Harvey describes nearly all connections, but still lacking the
microscopic capillaries (1600s). Proposes a closed circulatory system
pumped around by the heart
Judeo-Christian-Islam history
– Blood is life-giving, separates animals from vegetables
* In some other traditions, blood is sprinkled on seeds to ensure a good
harvest – though in other traditions, it’s just the opposite: spilt blood
makes the soil barren
– Turning Nile into blood was first plague wrought by Moses and
Jews could be spared the final plague by putting lamb’s blood
above their doors
– Old Testament carries instructions to not eat blood or meat
with blood, establishes a Kosher tradition
* ‘Eat not the blood, for the blood is the life’ Deuteronomy 12:23
– Qu’ran also includes verse forbidding eating of blood and is
part of Halal code
-– Transubstantiation: blood is wine/wine is blood
– Alchemy tradition? Lead into gold and the search for
the ‘elixir of life’: some secret way of turning
inanimate to animate
* Communion: drinking the wine is taking in the blood of
Christ
* The Holy Grail is a legend about the cup or chalice
supposedly used by Christ at the Last Supper
– Symbolically: the ultimate goal
Blood discoveries 1600s
- Jan Swammerdam probably made first microscopic observation of red blood
cells: ‘globules’, ‘corpuscles’ (1658?) - Microscopy, led by specialist Anton von Leeuwenhoek, describes cells and
capillaries (1674) - Marcello Malpighi actually describes these earlier, but the Royal Society’s
Philosophical Transactions publications propels Leeuwenhoek’s work further.
Malpighi also made the first description of fibrous, mesh-like feature found
in clotted blood, once the red corpuscles were washed away (1666) - Richard Lower shows air is acquired at lungs and
venous blood will turn bright red at lungs or when
let into a bowl (1600s) - Robert Hooke shows dissected dogs could be kept
alive by pumping air into lungs and noted difference
in venous vs. arterial blood (1600s) - vivisection - Robert Boyle, an alchemist interested in
transmutation (lead into gold), with others
(Christopher Wren, Richard Lower) performed
experiments on injecting dogs with various ‘liquors’
(1600s)
William Hewson
- William Hewson suggests linkage between thymus, spleen and
lymph for location of white blood cells, ‘central particles’ (1700s)
– emerging picture of the immune system - Also identifies role of lymph nodes in the drainage function for
body tissues and cavities. - He describes congealing process and suggests factors can
promote and inhibit this ‘coagulable lymph’ and it not simply
gelling at cold temperature. - Describes RBC as discs and not spheres.
- ‘the axillary glands are likewise frequently observed to swell in
consequence of cancers in the breast and it is found to be of no
use to extirpate the breast itself, unless the infected glands can
likewise be removed; for otherwise the cancerous humor left in
the glands may renew the disease’ 1774
The Barber-Surgeon
- Bloodletting or bleeding is common procedure or
cure for a variety of sicknesses - First surgeons were ‘barber-surgeons’ (most
practiced as dentists too). They were crudely
trained to let blood and their blood-soaked
bandages and clothes posted outside their
business indicated best times to conduct bleeding.
Today, barbers still use red and white striped poles
to advertise.
– Christian clergy were banned from performing surgical
operations, so the task fell to barbers - Leeches were often used to keep the blood flowing
– Leeches secrete an anticoagulant, hirudin, that
prevents the clotting of blood and thus their ability to
keep feeding off the blood meal of the host
Transfusion and donation history overview
- Part of the story is the emergence of ‘natural
philosophers’ in Europe. This is the first name
for scientists. - Another part of the story is the competition
between the English and French to be the first
and the leaders of discovery - English ‘team’: Robert Boyle, Richard Lower,
Christopher Wren, Thomas Willis, Edmund King - Dogs are preferred subjects, and first experiments
are adding things to circulatory system and making
observations about promoting or reducing vigor - Suggestion at the Royal Society: “to let the blood of
a lusty dog into the veins of an old one, by the
contrivance of two silver pipes fastened to the veins
of such two dogs”
The Fountain of Youth – Is it in Blood?
- An approach that has been tried in the
modern era - Parabiosis – an experimental technique where
model organisms have shared blood supplies
by connecting their circulatory systems
– Most frequently performed with mice and rats - Plasma-rich treatment of injuries in sports has
been practiced for decades and it seems to
speed up the rate of repair and healing - What is in plasma or parabiosis transfers that
could enhance this activity? Would such
components be present in higher levels in the
young?
– One candidate: GDF1 - A company, Ambrosia, set up a clinical trial to test the effect of plasmabased treatments and now offers commercially available ‘treatment’
– Plasma donors are aged 16-25
– 1L transfusion = $5500 USD
– No controls were involved in this clinical trial
– From the company founder: “dramatically improves people’s appearance, their
memory and their strength. It’s sort of surprisingly effective.”
– It shut down in early 2019 due to FDA concerns and does not appear to be in
business at this date - Another company investigating this: Alkahest
- Suggestion is that factors in plasma can help to restore brain function, for
example the loss in cognition and memory that is common in Alzheimer’s
and other neurodegenerative diseases
Transfusion and donation history 1600s
- Richard Lower is probably the first to perform and document dogdog transfusion in 1665.
– Artery to vein joining of dogs of ‘equal bigness’ and it revives the weaker
dog - Jean Baptiste Denis of Paris reads of the experiment in Royal
Society’s Philosophical Transactions. Decides to attempt with
humans. - Denis first transfuses sheep’s blood into a young man with a fever
in 1667. - Lower conducts transfusion from a sheep into Arthur Coga, a
homeless man who is ‘a little too warm in the brain’ in 1667. - Both of these first animal to human transfusions are successful in
at least the recipients did not die and there is a bit of arguing
over who was really first. - Denis conducts several more trials, including a Swedish
nobleman who dies upon a second transfusion and
three transfusions of calf’s blood into Antoine Mauroy,
a reported madman, who also succumbs a few months
later. - While Lower conducted another successful transfusion
near the end of 1667, the deaths in France and
religious views on the practice ultimately lead to a ban
on transfusions in France, England, Spain, and Italy by
the pope in Rome. - Transfusions are not attempted again for more than
100 years. - The Mauroy death was preceded by what
looked like obvious signs of immune reaction
(kidney pain, urine black as soot, fever and
sweating) - Investigation of the Mauroy death showed
that he was poisoned with arsenic by his wife.
The wife was compelled to murder by local
physicians and bishops who were opposed to
the radical and heretical transfusion methods.
Transfusion and donation history 1700-1800s
- Philadelphia surgeon Philip Syng Physick may
have performed first successful human-human
blood transfusion. (1795) - James Blundell, after refining the technique in
dogs, is credited with first published humanhuman transfusion, although the patient dies
from unabated internal hemorrhaging. (1818) - Blundell notes that same species is crucial for transfusion, venous
blood will work, and even an amount less than the blood lost is
helpful. - Blundell develops important apparatus improvements: warm
bath collection, funnel, 3-way stopcock, impellor (syringe). - In the mid to late 19th century, milk infusion were tried again to
help with cholera and tuberculosis, not with great success. Saline
solution was eventually found to have less dire consequences. - Landois catalogs transfusion results from Denis and Lower until
1874, 1/3 of animal recipients are improved, while ½ of human
recipients are improved. - 3 main problems plaguing the procedure: infection, clotting,
immune reaction.
Blood compatibility
Blood type/Blood group History
- Karl Landsteiner (University of Vienna) is credited with first
resolving these compatibilities and devising the A, B, C (O) groups
(1901 and later) - Mixes serum fraction (plasma with clotting factors [proteins]
removed) with whole blood and conducts studies on large number
of samples - Serum (plural = sera) has some ‘anti’ factors that make it
incompatible and agglutinate the RBC (clump together) - In 1902, two of his pupils find the 4th blood group (AB) that is the
rarest (~2.5%) after sampling another 155 donors - Standard nomenclature devised in 1927: A, B, O, AB
- Landsteiner awarded 1930 Nobel Prize in Physiology and Medicine
- Reuben Ottenberg first to do transfusion with typed blood in
1907 at Mt. Sinai Hospital, NYC. - Epstein and Ottenberg, first suggest in 1908 that blood groups are
hereditary. Mendelian patterns of inheritance – including the AB
codominant form – are eventually established. - A case of O type reacting with another O type blood led to
identification of the Rh factor in 1939 by Philip Levine, another
Landsteiner pupil. - It was called Rh factor for the studies of Landsteiner (and
Weiner), who showed that the antisera produced in rabbits or
guinea pigs reacted to rhesus monkey blood, also reacted with a
human (Caucasian) population from NYC. - The Rh factor was associated with a case of fatal erythroblastosis
fetalis (hemolytic disease of the newborn).
Clotting problem
- How was this solved?
– Reduce time of transfer
– Or let it clot, remove clot, and then transfer - In 1914, Albert Hustin shows that sodium citrate will
prevent blood clotting (shown also by Luis Agote of
Buenos Aires)
– Oxalate and sulfate were also used by some - In 1915, optimum citrate concentration is determined
to be 0.2% by Richard Lewisohn - Also found that citrate-treated blood can be used
successfully even after a few days of refrigeration - In 1916, Peyton Rous and J.R. Turner
find that glucose-citrate
combination allows extended
storage: weeks - Oswald Robertson, sets up the
storage of O-type blood for
anticipated casualties in World War I - WWI, Spanish Civil War, and WWII
drive major efforts in developing
methods for more efficient blood
storage and transfusion
– e.g. Alsever’s Solution
Blood banking history
- Soviets develop first system for collecting and storing blood for
use in hospitals (1930s) - First ‘blood bank’ in US is established at Cook County Hospital
in Chicago in 1937 by Bernard Fantus.
– It was loaned at 100% interest: the recipient had to donate twice as
much upon recovery! - The plasma fraction alone was also found to be helpful for
victims of blood loss - New techniques continue to refine and define different
components of blood and their function - Plastic becomes material of choice (1950s)
- Glycerol addition enables long-term storage (years) of some
blood products (1960s)
Blood substitutes
- Saline and other balanced salt solutions
– Isotonic
– Non-toxic, sterile
– Glucose/dextrose - Albumin: blood volume builder (do you know how?)
- Coconut milk?
- Synthetic forms
– Hemoglobin substitutes, such as perfluorochemicals
– Recombinant hemoglobin
– Individualized components: e.g. Factor VIII, Factor IX, immunoglobulins
Vampirism and the Vampire legend
- Legend about dead or undead obtaining life, eternal life
by consuming blood - Origins of legend are likely quite old
- Not too different from zombie legend
- Like parasites?
- Popular stories from Eastern Europe later romanticized
in fictions from Western Europe, including perhaps most
well known: Dracula by Bram Stoker (1897) - Now, a standard part of pop-culture and metaphorical
meanings abound
Frankenstein
- Sharing of blood – mixing of parts and identities
- Frankenstein story (Frankenstein or the Modern Prometheus
by Mary Shelley, 1818) - Making a monster by reanimating the body or combining
body parts - Natural and unnatural combinations
- Stemmed from Victorian Era fears of scientific
experimentation - ‘playing god’ as did Prometheus when he stole fire from the
gods and shared it with humans according to Greek legend - Who is the monster?
Splenic anemia
– The spleen is an organ which took a long time to understand.
– Early understanding: it produced ‘black bile’ and swelled up
or enlarged in many situations, such as malaria and anemia.
– The spleen was considered the lymph node of the blood.
– Anemia itself was initially characterized by pale appearance,
lethargy, weakness, and more often described in women.
– Around 1900, new tools were used to diagnose the
condition: hematocrit and hemacytometer to quantify blood
cell levels. New techniques to stain cells were used to judge
quality.
– Thus, splenic anemia is an anemia case involving, or at least
suspected of involving, spleen dysfunction.
– William Mayo (founder of the eponymous clinic) are
proponents of splenectomy as the cure: anemia is relieved
or reversed since in many cases hematocrit/hemacytometer
analyses show increased blood cell numbers.
– Abdominal surgeons become arbiters of blood disease. A
new class of healers, and even explorers.
– As these surgeons grow in prestige and autonomy, there is
some resistance to this and the cases that fail to progress or
result in fatality start to reveal a true lack of understanding
of ‘splenic anemia’. Often, only short term benefits are
observed.
– As early as 1910, arguments are waged about regulation,
standardization and legal protection.
– Splenic anemia starts to be seen in new or other
designations: such as leukemia, kala-azar (leishmaniasis)
and almost all that remains are cases of ‘idiopathic splenic
anemia’ or in the words of William Mayo “put in the form
of an Hibernianism, incomplete knowledge is essential for
the diagnosis”.
– Eventually, the term and the disease are outmoded.
Aplastic anemia
– Diagnosis depended on post-mortem examination and
distinctive fatty appearance of bone marrow; i.e. lack of
healthy red marrow. Determined by a pathologist.
– Earliest debate was whether this anemia was due to
intrinsic or extrinsic causes, but soon there were enough
factory worker cases to tie it to benzol (benzene) exposure.
– Became an ‘industrial exposure’ or ’occupational health’
disease. Involves labor policies, industrial hygiene, and
public health oversight.
– Use of newer blood testing technologies (hematocrit,…)
add a new way to identify and define aplastic anemia
without post-mortem autopsy.
– Earlier detection would have more pragmatic benefits, not
biased about which cadavers and autopsies were
conducted, which were much more common among
indigent.
– Is it the same disease? Revealed a shift in pathology
thinking from the post-mortem or morbid anatomy realm
into the diagnosis and study of the living.
– Major founders of the field of pathology, William Osler and
others, viewed such a shift with skepticism. Diagnoses were
not accurate, too narrowly determined and done too hastily
- and should not be done by laboratory pathologists.
– Toxicologists also gain some credence. Professional identity,
ownership, and authority are what is at stake.
– Epidemiological evidence was slow to come, partly because
of reluctance of physicians and hospital professionals to
procure this information.
– Different disease names arise: aplastic anemia, chronic benzol
poisoning, benzol susceptibility, toxic paralytic anemia.
– Provided some rationale to bring together the different
decision makers and types of evidence, i.e. required an
institutional effort or undertaking.
– Meanwhile, the study of aplastic anemia cases also includes
attempted definitions of the susceptible or at risk people and
the susceptibility concept starts to sink into the medical,
clinical, and legal views for dealing with patients, workers,
and other populations.
Pernicious anemia
–described first in 1850s
–a case of anemia that in spite of remissions, inexorably became worse
until, nearly unavoidably, death resulted within a few months to years.
Diagnosis at death.
–Low red blood cell counts and megaloblastic appearance (large red blood
cells)
–Many cases also show gastroenterological symptoms and neural
degenerations: numb fingers, ataxic gait
–Eventually, its ‘cure’ results in the Nobel prize for Minot, Murphy and
Whipple
–George Whipple describes lack of erythropoiesis in pernicious anemia
(1922)
–George Minot and William Murphy prescribe ½ lb beef liver/day (1926).
Liver and a liver extract were found to cure some, though not all.
Coincides with other emerging pictures of nutrition linked to health and
the importance of vitamins (vital amines) in several conditions.
– This liver prescription morphed into the clinical description of the disease:
pernicious anemia is that anemia that can be cured with liver extract –
preferably, ‘liver extract no. 343’ from Eli Lilly & Co. Health status is based
largely upon hematocrit/hemacytometer quantifications.
– Product endorsement enters the medical and health care field. Signals a
commercialization or commodification trend in dealing with the sick: health was
something that could or had to be purchased. Medicine can be a profit-making
enterprise.
– Narrow focus on blood signs and symptoms meant that GI or neurological
concerns were not addressed – was this still a part of pernicious anemia?
– Pernicious anemia definition changes depending on the specialist.
– Pre-digested liver was found to cure some cases that were not cured with ‘liver
extract’. This suggest new or unnoticed aspect.
– In fact, the idea that a meat or liver component was necessary as well as some
function of the stomach was known in late 1880s: coined extrinsic factor (meat)
and intrinsic factor (body/stomach component).
– Minot was probably influenced by experiments of the Canadians Banting and
Best, who isolated insulin and revealed its connection with blood glucose
regulation. Sets a precedent for supplementing deficiencies. Minot was
administered purified insulin in 1922/3 and it may have saved his life.
– Liver fractionation (water soluble fraction G) identifies a component that is also
in yeast and green plants. Gets the name folic acid. Eventually discover that
vitamin B12 (aka cyanocobalamin) is essential for generating folic acid. (1940s)
– Both folic acid and vit. B12 are crucial for thymine synthesis, DNA replication, cell
replication, and hemoglobin synthesis.
– Vit. B12 is made by bacteria – in our GI tract and ruminant animals. So we can
ingest it or absorb it from our own intestinal flora. This is the ‘extrinsic factor’.
– By 1960s, ‘intrinsic factor’ is shown to be a glycoprotein made by gastric parietal
cells that aids in vit. B12 absorption in the small intestine. GI problem was finally
connected.
