Medical science events
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Historic events in medical science

Summary
Peter Medawar writes about key historic events in the evolution of medical science. 
The Threat and the Glory
In the collection of Peter Medawar's essays 'The Threat and the Glory' he frames medical science as conjectural, after Popper.  Science is viewed as a network of connected hypothetical models of what may be.  Experiments may cast doubt on a hypothesis.  Hence we
Walter Shewhart's iterative development process is found in many complex adaptive systems (CAS).  The mechanism is reviewed and its value in coping with random events is explained. 
learn from our mistakes and improve
.  He argues that creativity in science is based on hypothesis.  Particulars are key. 

Pre-scientific medicine
Initially there was little scientific basis to the ideas about how the human body worked.  In consequence both diagnosis and treatment were confounded by invalid
The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
models
and solutions.  Medawar illustrates how to cope with the situation with the example of Dr. Thomas, who trained in 1901, and avoiding prescribing treatments in line with recommendations from his medical school.  He was valuable to the patient, because of this therapeutic nihilism and, for his management of his nurses, and his empathy is the capability to relate to another person from their perspective.  It is implemented by spindle neurons.  It is context dependently mediated by estrogen.  It develops over time: Piaget's preoperational stage includes rudimentary empathy, Theory of mind supports the development; initially feeling someone's pain as one integrated being, then for them and eventually as them.  In adults, when someone else is hurt the anterior cingulate cortex, amygdala & insula activates projecting [scapegoating] to the vmPFC.  If the pain is physical the PAG activates and motor neurons for the area where the other person was injured.  The intertwining of the ACC amygdala & insula in adults results in attribution of fault even when there is none which can make it hard to step in and actually help.  But in seven-year-olds the activation is concrete: PAG and sensory & motor cortexes with minimal coupling to the rudimentary vmPFC.  In older children the vmPFC is coupled to limbic structures.  Ten to twelve year olds abstract empathy to classes of people.  By adolescence the vmPFC is coupled to theory of mind regions and intentional harm induces disgust via the amygdala.  Sapolsky explains adolescent boys are utilitarian and tend to accept inequality more than girls do.  But both sexes accept inequality as the way it is.  Sociopaths do not develop empathy. 
(including touching the patient) and control of the illness. 

Most diseases did not kill 100 per cent of sufferers, and those that survived often felt a debt to the doctor who treated them. Dr. Thomas by avoiding treatments, such as mercury, antimony and bismuth, also helped the odds of survival.  As such
This page reviews the strategy of setting up an arms race.  At its core this strategy depends on being able to alter, or take advantage of an alteration in, the genome or equivalent.  The situation is illustrated with examples from biology, high tech and politics. 
good doctors could build a practice and reputation
even prior to effective understanding of the operations of the human body.   But Medawar notes, doctors did not expect to be well remunerated financially.  Many of their patients could not pay immediately if ever. 

Oscler's razor
William Oscler of Johns Hopkins advocated the scientific approach to medicine that Thomas followed.  Initially he recommended focusing on diagnosis, and prediction of outcome (taking control of the illness), and how to work effectively with nurses.  Treatment was to be avoided, since Oscler knew all treatments had no legitimacy and were often dangerous. 

By 1930 additional science had been integrated:  biochemistry, physiology, microbiology, immunology;  But the training was still focused on recognition & classification of disease.  Treatment was still a very minor part of the training.  Medical students realized this by the fourth year.  Notably some diagnosis now allowed the treating doctor to recommend surgery.  Surgery had advanced, due to anesthesia is the temporary removal of sensation.  It can be local, regional or general. 
and aseptic technique, and was saving lives of those with serious infections. 

By 1937 medical labs and wards were working together to leverage newly identified legitimate treatments for diabetes mellitus, pernicious anemia, and certain bacterial infections.  The integration of animal testing, and clinical trials, with scientific hypothesis, and experimentation, and diagnosis generated a
Walter Shewhart's iterative development process is found in many complex adaptive systems (CAS).  The mechanism is reviewed and its value in coping with random events is explained. 
Shewhart cycle
capturing and leveraging effective treatments. 

While additional treatments appeared, such as for lobar pneumonia is an inflamed lung.  It can be caused by infection with viruses or bacteria, drugs and autoimmune diseases.  HAP, including VAP can be very troubling. , which was treated with antibodies is a y-shaped blood transported protein generated by the adaptive immune system's plasma cells, B lymphocytes, to accurately identify and neutralize pathogens such as bacteria and viruses that exhibit a matching antigen. 
, a series of ancient diseases were still problematic to treat: acute heart failure is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
  • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
  • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
, syphilis, typhus, plague, TB, consumption or otherwise TB, is mostly an airborn bacterial lung infection, but it can also infect the brain, kidneys and other parts of the body.  The only vaccine is still the BCG.  The deployment of antibiotics during the 1940s allowed effective treatment: Streptomycin.  Diagnostic tools for TB are insufficient.  And because TB grows slowly in walled off pockets in the lungs it takes many months of treatment for antibiotics to eradicate the infection.  TB benefits from compromised hosts and has benefited from HIV/AIDS.  TB is also leveraging the plasmids that now carry immunity to all current antibiotics.  In 2016 it is estimated to latently infect two billion people.  9.6 million worldwide became infected in 2014.  1.5 million people will die from TB in 2016.  Deaths from the disease have fallen drastically since 2000.  TB has been halted or reversed in 16 of the 22 countries: India (Sep 2016, Infection base estimate increased Oct 2016), Vietnam, Indonesia; that have the majority of cases.  But it is still the infectious disease causing the most deaths world-wide.  Nano scale drug delivery has the potential to push back on TB and is being actively researched (May 2016).   .  Correct diagnosis was also essential. 

The first legitimate treatment - Insulin
Medawar describes the history of Insulin regulates the metabolism of carbohydrates, fats and protein by signalling the absorption of glucose by fat, liver and skeletal muscle cells.  It is a peptide hormone generated in the islets of Langerhans beta cells of the pancreas.  Peter Medawar explains it was an early drug therapy success.  As manufacturers have shifted from products developed by extraction to biologics: Humulin, Lantus, Levemir; safety has improved.  But the US list price has risen steeply (Feb 2016, Jan 2017)
's extraction, validation of action, preparation, purification, standardization and marketing.  Insulin finally offered doctors a legitimate treatment for a significant disease.  Sufferers of diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections. 
would lose weight, become debilitated, have an intractable thirst, continually need to urinate and become succeptible to infections.  Diabetes would result in invalidism and early death. 

As early as 1889 Minkowsky and Mehring showed that pancreaectomy of dogs led to all the symptoms of diabetes.   Medawar explains that the pancreas's generation of powerful digestive enzymes, a protein with a structure which allows it to operate as a chemical catalyst and a control switch. 
had limited the collection of the diabetes treatment.  Banting, having read a paper on atrophy of the digestive pancreas caused by a stone in the pancreatic duct, proposed ligaturing the pancreatic duct.  He, and his assistant Best, demonstrated the extract was a successful treatment for induced diabetes in a dog.  J.J.R. Macleod consequently called in the resources of the pharmaceutical company Eli Lilly, and Dr. Collip to prepare, purify, standardize and market Insulin. 

Medawar also notes the initial success of the treatment was masked by the attribution to diabetes of deaths from secondary effects of long term diabetes suffering. 

Insulin's termination of therapeutic nihilism
Prior to insulin regulates the metabolism of carbohydrates, fats and protein by signalling the absorption of glucose by fat, liver and skeletal muscle cells.  It is a peptide hormone generated in the islets of Langerhans beta cells of the pancreas.  Peter Medawar explains it was an early drug therapy success.  As manufacturers have shifted from products developed by extraction to biologics: Humulin, Lantus, Levemir; safety has improved.  But the US list price has risen steeply (Feb 2016, Jan 2017)
's development, treatments prescribed by doctors were dangerous, and generally bad for the patents.  They included: cupping, bleeding, violent purging, raising of blisters, botanical extracts and immersion in iced, or hot, water.  One treatment for diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections. 
, based on the symptom of weight loss, was to give additional carbohydrates!  Consequently enlightened medical schools recommended a focus on diagnosis, control of the illness and avoidance of treatment.  Insulin presented medical practice with a first legitimate treatment. 

Sulphonamides and synthetic chemistry
The development of the chemical industry and in particular dye stuffs resulted in the development of sulphonamides.  It was noticed that these were effective treatments for some bacterial infections.  The production of these wonder drugs led to the
This page discusses the mechanisms and effects of emergence underpinning any complex adaptive system (CAS).  Key research is reviewed. 
emergence
of the pharmaceutical industry. 

Medawar notes how the
This page reviews the inhibiting effect of the value delivery system on the expression of new phenotypic effects within an agent. 
alignment
of science, medicine and the pharmaceutical industry then undermined work on other potential treatments.  In particular penicillin research was under funded by grant committees focused on synthetic drug research and development.  It was only bootstrapped with the help of the Rockefeller Foundation. 

Penicillin and Florey
Penicillin was a miracle drug when it first emerged, due to its broad impact on bacterial infection and low toxicity.  But Medawar notes that after Fleming's discovery of the effect, it was found to be very difficult to extract penicillin from cells in the quantities needed for the early trials.  It was Florey who built a pilot scale production plant at his school of pathology, and leveraged the knowledge and experience of the major pharmaceutical companies, particularly Merck, to ramp production.  This resulted in adequate amounts of standardized product.  However, Merck patented the shared processes, highlighting a recurring dilemma between science and commerce. 

Medawar reminds us that bacteria and fungi have been in an
This page reviews the strategy of setting up an arms race.  At its core this strategy depends on being able to alter, or take advantage of an alteration in, the genome or equivalent.  The situation is illustrated with examples from biology, high tech and politics. 
arms race
over
This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
evolutionary
time scales and it is to be expected that bacterial defenses to fungal penicillin would exist.  Sloppy use of penicillin would consequently select for resistant mutants. 

Hypothesis and disease causation
Medawar describes how the expanding scientific knowledge and diagnostics allowed the construction of hypothesis about disease causation.  For example it was hypothesized that multiple sclerosis was an auto-immune disease. 

































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