This Mortal Coil - Andrew Doig

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• The book This Mortal Coil by Andrew Doig examines the evolution of causes of death throughout human history.

• It explores death from various perspectives, including infectious disease, nutrition/diet, heredity, behaviors, accidents, violence, and modern causes like cancer and heart disease.

• The introduction focuses on Siena, Italy in the 14th century when the Black Death plague arrived. It describes the devastating effects through the firsthand account of Agnolo di Tura, who lost 5 children to the plague.

• Over 75% of Siena’s population died within 5 months as the disease overwhelmed the city. Society collapsed as people abandoned homes and fields. Plague was able to spread rapidly due to prior years of famine and overcrowded living conditions.

• The book aims to show how causes of death have changed dramatically over time. In the medieval period, plague, famine and war (“The Four Horsemen”) were the major killers. Now, modern causes like heart disease, cancer and stroke prevail in developed nations.

• It will examine death through various lenses including history, medicine, science, social factors and more to trace humanity’s progress in overcoming some of the deadliest influences that have shaped mortality for millennia.

The causes of death have changed significantly over time. In the past, many people died from accidents, violence or infectious diseases due to living in small groups without modern amenities. The establishment of farming and cities led to more security but also malnutrition and disease from close contact with animals and lack of sanitation.

In the late 19th century, it was discovered that diseases could spread through microorganisms, driving improvements in clean water, housing, and hygiene. This knowledge, combined with vaccines and drugs, caused a major decline in infectious diseases and rising life expectancy.

However, non-communicable diseases like cancer, heart disease and stroke became more prevalent as lifespans increased. Unhealthy modern lifestyles like poor diets, smoking, drugs and lack of exercise also contribute. Neurodegenerative diseases are also more common in the elderly.

Definitions of death have changed from focuses on breathing and heartbeat to brain death. A functioning brainstem is now seen as necessary to support life. New medical technologies may help defeat more causes of death in the future. In summary, causes of death have changed largely due to advances in sanitation, medicine and lifestyles.

• In 1592, the plague returned to London, killing an estimated 17,000 people including some of Shakespeare’s family members. This highlighted the need to track mortality rates.

• The Bills of Mortality were introduced in London in 1592 to record deaths by parish and cause. This marked the beginning of public health record keeping in England.

• “Searchers of the dead” were appointed in each parish to inspect corpses and determine the cause of death. This data was compiled into weekly Bills of Mortality.

• Searchers had little medical training and had to examine decomposing bodies, putting them at high risk of disease. Their job was unpleasant and they faced stigma.

• If a death was deemed plague-related, the household would be quarantined with dire consequences. So searchers faced pressures to avoid such designations.

• The Bills provided early public health surveillance, allowing authorities to respond to outbreaks. Readers could also use the data to assess safety of public places.

• Over time, the Bills expanded to record 60+ causes of death and started separating data by sex. This laid the foundation for modern disease surveillance efforts.

So in summary, the Bills of Mortality system pioneered the collection of standardized mortality data in England, critical for understanding and responding to public health issues like the plague.

• The passage compares causes of death recorded in Bills of Mortality from 1664 and 1665 in London. In 1664, the leading causes were natural like “aged” but in 1665 plague had surged, with deaths increasing dramatically from 393 to over 5,000 per week.

• It suggests searchers falsified some plague deaths as vague causes like “fever” to avoid mandatory quarantines. This shows the intermittent nature of plague outbreaks in London.

• John Graunt pioneered analysis of Bills of Mortality data in 1662. He estimated London’s population, which was previously wildly overestimated, and created the first life table to estimate life expectancy.

• Graunt found life expectancy was only around 15 years and childhood mortality was high. His work helped understand risks and was important for insurance and other financial industries dealing with risk assessment. It represented a major improvement over just guessing at basic population and mortality data.

• Graunt found that while burials exceeded christenings in London, suggesting a declining population, this was contradicted by increased building and subdivision of houses. He concluded London was being supplied by people from the countryside moving in.

• Graunt categorized causes of death from London burial records into diseases, injuries, etc. The largest group was diseases of young children. He noted deaths could fluctuate based on new diseases emerging or awareness changing.

• Standardizing death classification helped determine health needs and understand changes over time. Disagreements led to the International Classification of Diseases (ICD) being developed in the late 19th century.

• The ICD is now on its 11th revision and collects global death data to track the dominance of non-communicable diseases like heart disease and cancer over infectious diseases. Doctors use ICD codes on death certificates to standardize cause of death reporting worldwide.

Here is a summary of the key points about completing a death certificate form for someone who died from AIDS:

• The immediate cause of death would be listed as AIDS or an AIDS-related illness like pneumocystis pneumonia.

• HIV/AIDS would be listed in the section for contributing factors or conditions leading to the immediate cause of death.

• Coroners may be involved if the death was considered unnatural or suspicious in some way. They may order an autopsy to determine the exact cause of death.

• Relatives would need to register the death at a local register office to obtain an official death certificate.

• Data from death certificates is collected by national statistics offices and the WHO to analyze trends in causes of death and support public health efforts.

• Doctors have some discretion in what they list as contributing factors, to balance medical accuracy with family sensitivities if risky behaviors were involved.

So in summary, AIDS or an AIDS-related condition would be the primary cause, with HIV listed as a contributing factor, and local legal/registration procedures would need to be followed to issue an official death certificate.

• Life expectancy was much lower in ancient Rome and the Middle Ages compared to today. In Rome, high death rates were due to ineffective medicine against diseases, poor nutrition, lack of sanitation, and diseases spreading rapidly along trade routes.

• In the Middle Ages, estimates put average life expectancy between 30-40 years. Records of the English king Edward I show his wife Eleanor had 16 children but many died young, demonstrating high child mortality.

• Data from France since 1816 shows a doubling of life expectancy from around 40 to over 80 currently. Major events like wars caused dips while improvements in medicine, nutrition, and sanitation led to steady increases over time.

• Comparisons to current developing countries show that places like Sierra Leone and Afghanistan now have higher life expectancies than France did in the past. This reflects overall global improvements in population health over the last century.

• A few hundred years ago, improved living conditions, sanitation, nutrition, and reductions in disease mortality rates in Europe and North America allowed populations to grow steadily without triggering famines.

• Once people had confidence their children would survive to adulthood and they would be cared for in old age, families tended to have only two children on average rather than many to account for high child mortality.

• This demographic transition from high birth/death rates to low birth/death rates led to a period of rapid population growth as death rates fell before birth rates declined to match.

• Most developed countries have now completed this transition and have stable populations with high life expectancies, low infant mortality and fertility rates below replacement level. However, this took different amounts of time in different places.

• The summary gives examples of Japan, Brazil, and Ethiopia at different stages of demographic transition from 1960-2017 to illustrate this process over time in different world regions.

• The US health system has excessive administrative costs and high levels of inequality in health spending. Homicide and suicide rates are high due to easy gun availability. Child mortality and maternal death rates are also high compared to other rich countries.

• While greater wealth is correlated with better health outcomes, spending alone does not explain improvements. Medical advances not tied to income, like public health interventions and antibiotics, accounted for 75% of health gains from 1930-1960.

• The relationship between income and health holds for both countries and individuals. However, psychological stress from low social status may also impact health by worsening the immune system and leading to risky behaviors. Greater inequality in a society could therefore lead to poorer overall health.

• To generally increase health, a more equal society may be needed, as simply increasing overall wealth is not sufficient. Vaccination and other cheap medical advances can improve health without income growth. Hunter-gatherer lifestyles andtransitions to agriculture are also briefly discussed in historical context.

There were several factors limiting population growth despite increased food production and higher birth rates during this period:

1. New infectious diseases emerged as humans started living in close proximity to farm animals. Zoonotic diseases like measles, influenza, tuberculosis, etc. spread rapidly in dense agricultural communities and cities. This acted as a check on population growth.

2. Epidemics were common as these new diseases ravaged populations that had no natural immunity. Entire cities could be devastated. This led to frequent collapses of early civilizations and population losses.

3. Poor sanitation and lack of reliable healthcare in dense urban settlements contributed to infections and diseases like diarrhea. This undermined overall population health.

4. Dependence on just a few crops or animal species meant disease outbreaks in those could cause widespread famines, reducing populations.

5. Regular disease exchange occurred as contact increased between disconnected communities through trade, warfare, etc. This triggered new epidemics as populations lacked immunity to each other’s disease pools.

So in summary, while food production increased carrying capacity, regular epidemic cycles of new pathogens maintained population sizes close to levels sustainable with existing resources and technologies until immunities built up over millennia. Disease was a major limiting factor restricting rapid population growth.

The Plague of Justinian spread throughout the Byzantine Empire and beyond in the 6th century due to war and trade routes. It significantly weakened the empire by reducing the population and workforce. Abandoned farms led to famine, while lower tax revenues impacted the government. Subsequent outbreaks over the next 200 years also spread via long-distance travel along trade routes. The eighth-century Arab conquests were perhaps enabled by the depopulated states of Byzantium and Persia. Centuries later, the Black Death pathogen reached Europe in 1347 via trade routes from Central Asia, carried by flea-infested rats on merchant ships to Mediterranean ports. It then swept across the continent, killing an estimated 30-60% of the population and severely impacting societies for years after. Transmission was aided by increased trade and travel under the Mongol Empire.

• The Black Death plague pandemic of 1347-1351 was the worst natural disaster in European history, killing up to 60% of the population. In some densely populated areas, over 80% of people died.

• Its impact was devastating - villages, industry and farmland were abandoned. Surviving peasants saw improved wages and social status as their labor became more valuable. Many moved to towns.

• Religious and superstitious responses like giving money to the Church, self-flagellation, and persecution of Jews did not stop the disease. This undermined the credibility of the Church.

• Early isolation and quarantine practices began in Italian cities like Ragusa (modern Dubrovnik) in the 14th century. A 30-day isolation period called a “trentino” was introduced. This later became known as “quarantine” and was extended to 40 days.

• Quarantine systems proved effective at controlling outbreaks, though plague still reappeared occasionally when precautions slipped, like a major outbreak in Marseille in 1720 that killed 50,000 people despite their quarantine practices.

• A third pandemic started in Yunnan, China in the 1850s and spread through Asia, Africa, the Americas and elsewhere, killing over 12 million Indians alone by the early 20th century. This allowed scientific investigation of the plague bacterium.

• Robert Koch helped discover the causes of many infectious diseases like tuberculosis, cholera, typhoid, diphtheria, tetanus, leprosy, gonorrhoea, syphilis, pneumonia and meningitis in the late 19th century. He proposed a set of criteria (Koch’s postulates) to establish a microorganism as the cause of a disease.

• In 1894, Alexandre Yersin and Shibasaburo Kitasato were sent to Hong Kong to investigate the plague. Using Koch’s postulates, they both successfully isolated and cultured the plague bacterium (Yersinia pestis) from victims. Yersin’s work was more thorough and the bacterium is now named after him.

• Paul-Louis Simond continued this work in India in 1897. He discovered that rats and their fleas spread plague, through experiments transmitting it between infected and healthy rats via fleas. This helped explain plague outbreaks.

• DNA analysis of plague bacteria from archaeological sites of past pandemics like the Black Death and Plague of Justinian showed they were caused by distinct Y. pestis strains, helping explain differences in symptoms. Ancient DNA analysis is unraveling the long history of plague in humans.

• Trading networks in prehistoric Europe connected large settlements thousands of miles apart, though the languages spoken are unknown.

• The Trypillia culture in Ukraine collapsed around 5,400 years ago when their large towns were abandoned and burned. This Neolithic decline was likely due to a devastating plague epidemic.

• Ancient DNA sequencing has found evidence of an ancient Yersinia pestis plague strain (Gok2) in remains from a 5,000 year old mass grave in Sweden, providing direct evidence of plague before modern times.

• Gok2 and other ancient plague strains coincided with the decline of Neolithic populations across Europe. This suggests plague was a factor in the collapse of civilizations like the Trypillia culture.

• Y. pestis periodically caused epidemics by jumping from rodents to humans throughout history. It remains a risk today as the bacterium lives worldwide in rodents and can evolve new antibiotic resistant strains.

• Smallpox was a devastating disease that killed around 30% of those infected, with even higher rates in infants and young children. Wealth and social status provided no protection against the disease.

• An early method of preventing smallpox was variolation, where matter from smallpox blisters was deliberately introduced to induce a mild infection and confer immunity. This practice spread from Asia to Europe and the Americas in the 17-1800s.

• Edward Jenner developed the safer practice of vaccination using cowpox virus in 1796 after observing that milkmaids exposed to cowpox did not get smallpox. Subsequent experiments showed vaccination with cowpox conferred immunity to smallpox.

• Jenner’s discovery was adopted widely in Europe and then spread globally through initiatives like those led by Francisco Javier de Balmis to vaccinate over 100,000 people across Central and South America, Mexico, and Asia in the early 1800s.

• Compulsory vaccination programs led to the eradication of smallpox in most countries by the 1950s. The WHO intensified global vaccination efforts from 1967-1977, finally eradicating smallpox worldwide with the last case reported in Bangladesh in 1975. Coordinated global vaccination was key to ridding the world of this devastating disease.

• The island where she lived was vaccinated within a 1.5-mile radius of her home immediately after she contracted smallpox.

• Within five miles of her home, each house, area where people might congregate, school and healer was visited by a team from the Smallpox Eradication Program to check for additional cases.

• None were found, and the woman named Rahima made a full recovery.

• The last person to have naturally acquired smallpox was Ali Maow Maalin, a hospital cook in Somalia in 1977. To contain the potential outbreak, over 54,000 people were vaccinated in the area in the two weeks following his diagnosis.

• Extensive containment measures were taken, including quarantining contacts, vaccinating residents and closing facilities. The efforts were successful and no additional cases were found.

• In the 19th century, towns like Liverpool and Manchester in England grew rapidly during the Industrial Revolution as people moved from rural areas for work. However, housing and sanitation infrastructure did not keep up with the population growth.

• Overcrowded slums with unsanitary living conditions became breeding grounds for diseases like typhoid and typhus. Housing was unsafe, with many people living in cellars or multi-family homes without running water or sewage systems.

• Nightsoil workers manually collected and removed human waste, but this service was not always available to the poor. Waste was often disposed of improperly in streets or courtyards where children played.

• When appointed as the first medical officer of health in Liverpool in 1847, William Duncan found the city to be extremely unhealthly. Many slum housing inspections revealed deplorable conditions like families living above sewage wells.

• Without proper public health interventions, diseases spread rapidly in the unsanitary living environments of 19th century industrial city slums. This highlighted the need for improved housing, water, and sanitation infrastructure to support growing urban populations.

• In the early 19th century in England, the rich had an unhealthy diet high in meat and low in vegetables, while malnutrition was widespread.

• Life expectancy varied greatly based on location and occupation. In 1843, professionals in rural Rutland lived until age 52 on average, while laborers in industrial Liverpool only lived until age 15.

• Major killers at the time were infectious diseases like tuberculosis, typhoid, smallpox, measles, and pneumonia.

• Data from 1840-1910 shows dramatic declines in deaths from these diseases as public health improved. For example, smallpox deaths fell from over 10,000 to just 19. Life expectancy increased by 11 years for men and 13 years for women over this period.

• Diseases like typhus thrived in overcrowded, unsanitary living conditions for the poor. Efforts like opening public bath houses and improving sanitation helped reduce typhus and other infectious diseases.

• Advances in understanding transmission of diseases and developing vaccines also helped control smallpox, typhus, and other illnesses over the late 19th-early 20th century. Overall living standards and public health improved significantly.

• Dr. John Snow was a physician in London in the 1850s who was convinced that cholera was spread through contaminated drinking water, not “bad air” as the prevailing theory claimed.

• In 1854, a major cholera outbreak occurred in the Soho neighborhood of London. Through investigating the outbreak, Snow found that nearly all victims obtained their water from a particular public water pump on Broad Street.

• This helped prove Snow’s theory that contaminated water, not miasma, was the main means of spreading cholera. While contaminated water pumps could spread the disease, improving sanitation systems for washing, cooking, and sewers helped make outbreaks less deadly, as seen when cholera returned to Liverpool in 1854.

• Snow’s pioneering work in identifying contaminated water as the cause of cholera outbreaks transformed public health approaches and set an example for how living conditions for the poor could be improved through better sanitation infrastructure and clean water access. This helped reduce future cholera epidemics.

• In 1854, a cholera outbreak broke out in the Soho district of London. John Snow investigated and found that the outbreak was centered around a water pump on Broad Street.

• Snow mapped the locations of deaths from cholera and found they clustered around the Broad Street pump. His evidence suggested the contaminated water from this pump was spreading cholera.

• The handle of the Broad Street pump was removed on Snow’s recommendation, and the outbreak subsided. However, Snow’s waterborne theory of cholera transmission was still controversial at the time.

• Filippo Pacini had also identified the cholera bacteria (“Vibrio cholerae”) under the microscope in 1854 in Italy, but his findings were not widely recognized.

• In 1883, Robert Koch isolated and cultivated the cholera bacteria, providing further convincing evidence that Snow and Pacini were correct about cholera being caused by a waterborne pathogen.

• Snow’s identification of the specific contaminated water source through careful investigation and mapping is now seen as a pioneering study in epidemiology and evidence-based public health intervention.

So in summary, Snow used epidemiological methods to trace the 1854 Soho cholera outbreak to a single contaminated water pump, supporting his theory that cholera spreads through water and helping end the outbreak, though bacterial causes were still controversial until Koch’s studies.

Giving birth upright became difficult for humans because evolving to walk on two legs led to structural changes that compromised the birth canal. This made childbirth painful and dangerous, requiring assistance.

Historically, untrained midwives attended home births with low mother mortality. However, when doctors began overseeing births in the 17th century, infection rates soared as they spread germs between patients. This “childbed fever” killed many new mothers.

In 1843, Oliver Wendell Holmes published evidence that doctors were transmitting the deadly puerperal fever between patients. However, the medical community resisted this idea. Ignaz Semmelweis later conducted an important study at a Vienna hospital with two maternity wards - one staffed by midwives and one by medical students. The ward with students had a 10% mortality rate while the midwife ward was under 4%. This convinced Semmelweis that doctors were bringing infections from autopsies to laboring women. His work established the importance of handwashing and hygiene in obstetric care.

• In the 19th century, Dr. Ignaz Semmelweis observed that women giving birth at hospitals with medical students had much higher mortality rates from childbed fever than those at hospitals without students.

• He realized medical students were carrying infection from autopsies to birthing mothers without washing hands. He introduced a policy of handwashing with chlorine solution after autopsies.

• Mortality rates dropped dramatically, by as much as 18%. Some months had no deaths at all.

• However, Semmelweis’ views were rejected by the medical community. He was driven out of his job and died in an asylum.

• It took 20 more years for his work on infection prevention to be rediscovered and his reputation rehabilitated. Formal acceptance came with germ theory and acceptance of antiseptic techniques in the late 19th century.

• Measures like midwife training and certification, as well as public health improvements in sanitation and nutrition, further reduced mortality rates from childbed fever and infant mortality over the following decades.

• Penicillin was finally able to defeat the bacterial cause of childbed fever in the 1930s, making death in childbirth now very rare. Semmelweis’ insight into preventing infection through handwashing saved countless lives.

• The French led by Ferdinand de Lesseps attempted to build a Panama Canal in the 1880s, following their success with the Suez Canal. However, the Panama project failed due to construction issues, lack of funds, and most significantly, malaria and yellow fever epidemics spread by mosquitoes. Over 20,000 workers died.

• Yellow fever and malaria were the biggest obstacles to building the canal. Yellow fever was endemic in Panama and spread by the Aedes aegypti mosquito. Malaria was also widespread and caused by Plasmodium parasites transmitted through Anopheles mosquitoes.

• Carlos Finlay first proposed in 1881 that yellow fever was transmitted by mosquitoes, but his experiments failed to conclusively prove it. The role of mosquitoes as vectors for malaria transmission was revealed in the late 1890s by researchers discovering malaria parasites in mosquito guts.

• Persistent malaria and yellow fever epidemics ultimately led to the collapse of the French Panama Canal project in 1888 and bankruptcy of the company. This demonstrated the devastating impact mosquito-borne diseases could have through spreading epidemics among workers.

• During the Spanish-American War of 1898, yellow fever spread rapidly among American troops invading Cuba, sickening 75% of troops and causing over 5,000 deaths from disease like yellow fever, more than were killed in combat.

• A commission was set up to find a solution. They confirmed Cuban scientist Finlay’s hypothesis that yellow fever is transmitted by mosquitoes, specifically the Aedes aegypti mosquito.

• Major William Gorgas eliminated yellow fever from Havana by isolating patients, eliminating mosquito breeding sites, and spraying insecticide. This proved mosquito-borne transmission could stop yellow fever.

• This success was crucial for the Panama Canal project, as the isthmus was infested with malaria- and yellow fever-carrying mosquitoes, which killed many French workers. Gorgas was sent to make the canal zone safe. He drained swamps and treated all standing water with insecticide to eliminate larvae, screened buildings, and quarantined sick workers. Within two years malaria was eliminated.

• The canal opened in 1914 after overcoming enormous engineering challenges. It demonstrated how targeting mosquitoes could prevent deadly tropical diseases during large-scale infrastructure projects.

• The Duffy-negative gene protects against P. vivax malaria and is common in sub-Saharan Africa and parts of Asia/Latin America. It was introduced to the Americas by slaves from Africa.

• People in India/Southeast Asia are not Duffy-negative likely because the ancestral strain of P. vivax was introduced there before the Duffy-negative gene evolved in Africa 30,000 years ago.

• Being Duffy-negative comes with costs like increased cancer risk. It provides no protection against P. falciparum, the deadlier malaria parasite.

• Instead, populations evolved other mutations like sickle cell, thalassemia, G6PD deficiency that protect against P. falciparum despite serious health risks. These persist because malaria is such a debilitating disease.

• Progress has been made against malaria through eradication programs, drugs, bed nets, but it remains a challenge in parts of Africa. Novel approaches like vaccines and genetically engineered mosquitoes are being explored but also raise ethical concerns if released. Widespread eradication could transform many developing nations.

• In his influential 1798 book “An Essay on the Principle of Population”, Thomas Malthus argued that population levels are controlled by the availability of resources, especially food production.

• If food supply can easily support a population, it will increase. But the food will then need to be divided among more people, worsening their living standards. Many will fall into “severe distress.”

• According to Malthus, distress includes diseases like epidemics and plague, as well as famine, which “levels the population with the food of the world.”

• Efforts to increase food production can only provide temporary relief, as population will eventually outstrip food supply again.

• The ultimate check on human population growth is simply running out of food. Famine is therefore seen as “the last, the most dreadful resource of nature” and an inevitable part of the human condition, according to Malthus’ theory.

• Malthus argued that population is limited by food supply and will lead to misery or vice when population exceeds food availability. Western Europe’s records over the past 1,000 years provide evidence for this.

• Famines were common in Europe from 1250-1345 before the Black Death, when populations were at the limit of food resources. Fewer famines occurred after the Black Death reduced populations.

• Prolonged bad weather like the heavy rains from 1315-1317 caused widespread crop failures and livestock deaths, resulting in famine that killed 10-25% of northern Europeans.

• Volcanic eruptions like Iceland’s Laki volcano in 1783 also caused famines by damaging crops with toxins over vast areas for years. Its effects may have killed as many as 6 million people across Europe and Egypt.

• During famines, people resort to consuming almost anything to survive, including rats, zoo animals, tree bark, leather, etc. This often caused disease and more deaths. Desperate measures included selling children, cannibalism, and swapping or eating one’s own children in extreme cases of starvation.

So in summary, Malthus was generally correct that populations in pre-modern times were vulnerable to food shortages caused by weather or natural disasters, which often led to widespread famine and population declines until resources recovered. Records support cyclical periods of famine linked to maximized local populations.

• The fairy tale Hansel and Gretel depicts the horrors of famine, including child abandonment, poverty, slavery, cannibalism, and murder. It may have originated during a famine in Germany in 1315.

• During starvation, the body first burns glycogen stores, then fat, and finally proteins. This leads to physical symptoms like weakness, muscle wasting, organ damage, infections, etc.

• A 1944 study at the University of Minnesota examined the psychological effects of starvation. Subjects became obsessively preoccupied with food and lost interest in other activities. They withdrew socially and showed signs of depression, anger, and psychosis.

• In real famines, social breakdown can occur as survival instincts take over. Crime increases as people steal food, and extremes in behavior emerge like cannibalism, child abandonment, suicide, and migrations in search of food.

• Famine was historically a major factor controlling human population levels, as Thomas Malthus argued. However, something changed after 1650 as populations grew without corresponding famines in some places, showing the link between overpopulation and famine had been broken.

• In the 1600s, the Dutch established independence from Spain after the Eighty Years’ War. Their Protestant north became the Netherlands and benefited from skilled immigrants.

• The Dutch economy boomed in shipping and trade, making them world leaders in art and science by the 1700s. The Dutch East India Company helped them dominate Asian trade.

• The Dutch developed important financial tools like stock exchanges and central banking. They stored grain imports to cope with bad harvests.

• By draining land and using windmills, the Dutch excelled at land reclamation, increasing farmland. They also established early welfare programs.

• In the 1700s, agricultural improvements like crop rotation and selective breeding in Britain and the Netherlands boosted food production. New commodities from the Americas diversified diets.

• Pioneers like the Bridgewater Canal precipitated British canal and railway building, revolutionizing transport. Canals helped trigger an agricultural boom.

• Economists like Malthus predicted famines from overpopulation, but advancements in farming outpaced population growth, avoiding catastrophes as predicted. Amartya Sen later showed famines are often caused more by access issues than simple food shortages.

• The Bengal famine of 1943 was avoidable as India had sufficient food, but many rural laborers lost jobs and incomes amid rising food prices, causing widespread starvation. The British authorities failed to take effective action to prevent the famine, as their priority was defending India from a potential Japanese invasion.

• Amartya Sen argued that famines are economic disasters caused by lack of access to food, not just food shortages. Social and economic factors like declining wages, unemployment, and poor distribution can lead to starvation within societies even when food exists.

• Sen’s theory was supported by the Great Chinese Famine of 1959-1961, caused by Mao Zedong’s policies during the Great Leap Forward. China kept the catastrophe secret due to lack of press freedom and opposition.

• Sen found that modern famines tend to occur in authoritarian states, while functioning democracies with a free press have not experienced famines, as governments are incentivized to address crises to avoid public backlash.

• World War I saw deliberate attempts to starve civilian populations through naval blockades. The British blockade severely impacted food access in Germany, contributing to hundreds of thousands of deaths and social unrest by 1917-1918 as rations declined drastically. Morale and health suffered tremendously by the end of the war.

• The blockade of Germany during WWI continued even after the fighting stopped in 1918, and was used to pressure Germany to sign the Versailles Treaty. It ended in July 1919. Estimates of deaths from starvation and related illnesses during/after the blockade range from hundreds of thousands to over 700,000.

• During WWII, Churchill sought to win indirectly by bombing German cities. The US joined in bombing campaigns and also mined Japanese shipping lanes to disrupt food transport, called “Operation Starvation.”

• Data from 1914-1924 on the heights and weights of nearly 600,000 German schoolchildren showed effects of malnutrition, with 1918 being the worst year. Children remained shorter their whole lives. Upper-class children fared better with access to black market food.

• Relief efforts by charities and Herbert Hoover’s US Food Administration helped provide food and aid to German children after WWI ended. Their health improved by 1923.

• In the 1990s, North Korea experienced a severe famine estimated to have caused hundreds of thousands to several million deaths, due to loss of fuel and fertilizer aid after the USSR collapsed, combined with flooding and cuts to food rations. The government has never acknowledged the famine.

• In the 18th century, chronic malnutrition was common even for those not facing famine, as diets lacked essential nutrients. Poor food quality could lead to disease even when calories were sufficient.

• Average daily calorie intake in France/England was very low (~2,100 calories in 1700 England, less in France), barely enough for basic bodily functions. Most energy went to just staying alive rather than work.

• People were short and thin due to lack of calories and nutrients in childhood. Small bodies required less food to survive. They were chronically stunted with higher disease risk.

• Chemical analysis in the late 18th century showed calories provide energy, but other nutrients in food may also be essential. It was unclear if single staples like rice/potatoes could provide complete nutrition.

• By the late 18th/19th century, average calorie intake and standards of living gradually increased in western Europe. Taller, healthier populations were better able to work productively and improve their situation over generations.

So in summary, while calorie intake increased food security, the new science began questioning if calories alone ensured good health and highlighted the potential role of other nutrients from a diverse diet. Chronic malnutrition and disease risk remained issues even after famine risk receded.

• Scurvy was a disease that afflicted sailors and others on long sea voyages, causing bleeding gums, joint pain and death. It was caused by a lack of vitamin C in the sailors’ diet of salted meat and hardtack biscuits.

• In 1747, Scottish naval surgeon James Lind conducted an early clinical trial on crew members with scurvy. He divided them into groups testing different hypothesized remedies, and found that the group given oranges and lemons recovered quickly, showing citrus prevented scurvy.

• However, Lind did not fully recognize the significance of his discovery. In his 1753 treatise on scurvy, he buried the key findings and recommended other questionable therapies. He also proposed preserving citrus juice by boiling it into a rob, not realizing this destroyed the vitamin C.

• While Lind discovered citrus prevents scurvy, systematically through a controlled trial, full implementation of regular citrus intake on ships took longer. Scurvy continued afflicting long sea voyages until theimportance of Lind’s discovery was fully realized in preventing the disease through diet.

• In the late 18th century, British naval surgeon James Lind conducted experiments that showed consuming citrus fruits prevented scurvy. However, his findings were not widely implemented.

• In 1793, the HMS Suffolk demonstrated that giving sailors small daily doses of lemon juice prevented scurvy outbreaks. This led the Royal Navy to issue lemon juice rations in 1795, effectively eliminating scurvy.

• Later in the 19th century, a switch from lemons to limes resulted in scurvy returning, as limes have much less vitamin C. Antarctic explorer Robert Scott’s expedition in 1911 suffered from scurvy.

• Early 20th century animal experiments helped discover vitamins were essential micronutrients. Guinea pigs developed scurvy-like symptoms when fed grain-only diets, but were cured with vitamin C sources. This linked vitamin C deficiency to scurvy.

• Many common deficiencies like vitamin A, iron, iodine and zinc persist globally and especially impact children and pregnant women. However, fortifying foods can easily treat and prevent these deficiencies.

• Obesity rates have increased significantly worldwide over the past few decades due to changes like reduced physical activity at work and increased availability of highly processed foods.

• Historically, being overweight was seen as a sign of wealth and prosperity since food scarcity was common. Today the reverse is true due to overconsumption.

• The Pacific islands and Middle East have some of the highest obesity rates globally. Factors contributing to this include adoption of Western diets high in fat/sugar and reduced physical activity.

• For Pacific Islanders, generations of long ocean voyages without knowing when food sources would be found may have selected for genetic traits favoring fat storage, helping explain current obesity tendencies. This supports the “thrifty gene” hypothesis that such genes were beneficial in past eras of famine but detrimental now.

• Addressing obesity is important for individual and public health. Countries like Kuwait are trying strategies like bariatric surgery to combat sharply rising rates of diet-related diseases like diabetes.

• The thrifty gene hypothesis proposes that genes for fat accumulation evolved as an adaptation to survive famines, but evidence for it is unconvincing. It’s difficult to separate genetic and cultural factors.

• A better explanation is that mutations causing obesity were not previously disadvantageous because humans eliminated large predators that would target obese individuals. This allowed such mutations to accumulate in the gene pool.

• Studies show genetics play some role in obesity, with hundreds of gene variants each having a small effect. Some variants may confer benefits in addition to obesity risk.

• Obesity has many negative health impacts like increased risk of heart disease, cancer, diabetes, respiratory problems, osteoarthritis, kidney disease, and mental health issues. It reduces life expectancy significantly.

• The modern obesity epidemic can be seen as a case of maladaptation, where behaviors and physiology adapted for ancestral environments are mismatched with current environments rich in sugars, salts, and disrupted circadian rhythms. This drives overconsumption and weight gain.

• Woody Guthrie was a famous American folk singer known for songs about the Great Depression and working class struggles.

• In the late 1940s, Guthrie started exhibiting disturbed behaviors like stumbling, forgetfulness, and personality changes. This led to his eventual diagnosis of Huntington’s disease.

• Guthrie’s mother Nora also died of Huntington’s disease at age 41. She had displayed violent behaviors before her death.

• Huntington’s disease is inherited in an autosomal dominant pattern, meaning only one parent needs to pass on the mutation for a child to develop the condition. Studying Guthrie’s family history helped uncover this inherited nature of the disease.

• Woody Guthrie passing away in 1967 provided an opportunity for researchers to study the genetics of Huntington’s disease by examining his DNA and tracing it through affected family members. This eventually led to discovering the location of the Huntington’s disease gene, one of the first genetic disease genes to be found.

• The person describes experiencing uncontrollable twitching and movements of their arms and hands that they cannot control. Their wrists feel weak.

• Doctors have asked about how their mother died of Huntington’s disease (also known as Huntington’s chorea at the time). However, the doctors have not clearly explained if the disease is hereditary or not.

• The person wants doctors to be clearer in their explanations so patients can better understand what may be wrong with them. If it’s not caused by alcohol, they wonder what else it could be.

• Huntington’s disease is a genetic dominant disorder caused by a mutation in the huntingtin gene. It causes progressive movement, cognitive and psychiatric problems.

• The disease is fatal, with a 15-20 year life expectancy after symptoms start. It typically appears between ages 30-50. Woody Guthrie suffered from Huntington’s disease.

• The disease is inherited if one parent has the mutated gene, as it is dominant. The pattern of inheritance was accurately described by Dr. George Huntington in 1872.

• Meiosis is the process by which germ cells like eggs and sperm are formed with only half the normal DNA amount, allowing for sexual reproduction and genomic diversity. It was first observed in sea urchin eggs in 1876.

• In the early 20th century, biologists proposed that chromosomes carry genes and are inherited from parents, providing a mechanism for Mendel’s laws of heredity. But little was known about specific disease genes.

• Milton Wexler co-founded the Hereditary Disease Foundation in 1967 to fund research on Huntington’s disease, which was affecting his ex-wife Leonore and her family.

• In the 1970s, the Foundation discovered an isolated village in Venezuela with thousands affected by Huntington’s disease all tracing back to a common ancestor. This provided an ideal population for genetic research.

• In the 1980s, an international collaboration conducted linkage analysis in the Venezuelan families, successfully mapping the Huntington’s gene to chromosome 4 - a major breakthrough and an early example of discovering a disease gene’s location. This paved the way for future gene mapping and sequencing efforts.

The discovery of a rare genetic disease called fumarase deficiency in a community in Colorado City, Arizona/Hildale, Utah revealed the effects of extensive inbreeding practices among members of the Fundamentalist Church of Jesus Christ of Latter-Day Saints (FLDS). Founding families encouraged marriage between close relatives to preserve “pure bloodlines”. This led to numerous cases of fumarase deficiency, a serious condition caused by mutations in the fumarase gene. Other genetic disorders also emerged due to the high degree of relatedness between parents in the community. Examples of harmful inbreeding illustrate why laws prohibiting incestuous relationships exist in most societies.

• Attitudes towards cousin marriage vary widely around the world, with laws and social norms differing in different regions. It is common in the Middle East but less accepted in parts of Europe, Asia, and America due to health risks.

• Cousin marriage rates in places like Saudi Arabia are very high (over 70%), exacerbating genetic diseases due to increased inbreeding over generations. Countries are now offering genetic screening to couples.

• A global study found cousin marriage negatively impacted traits like height, lung function, and IQ, equivalent to 10 months less education and 1.2 cm shorter height. No effect on other traits was found.

• French Canadians descend from a small group of filles du roi (King’s daughters) women brought over in the 1600s to increase population, leading to founder effects and genetic diseases today.

• Native Americans trace to a small ancestral population that crossed into Alaska during the last ice age, resulting in low genetic diversity despite their large populations historically, making them vulnerable to European diseases.

• Population bottlenecks from disasters, war, etc. can sharply reduce genetic diversity in groups for future generations, as seen in the Hutterites and estimates that half of people may carry lethal recessive mutations. Screening and avoiding cousin marriage can help prevent diseases.

• In 1901, Alois Alzheimer examined a patient named Auguste D who was exhibiting symptoms of cognitive decline such as memory loss, difficulties with language, and erratic behavior.

• After her death in 1906, Alzheimer performed an autopsy on her brain and found abnormalities - dense structures and deposits - that were unlike anything he had seen before. This defined the tau tangles and amyloid plaques that are characteristic of Alzheimer’s disease.

• Though Alzheimer had described just one case, it was believed to represent a new disease called Alzheimer’s. However, it was initially considered a type of “presenile dementia” since Auguste D showed symptoms at a relatively young age of 51.

• Senile dementia in old age was commonly viewed as a normal part of aging and was neglected. Mental illness in general also lacked attention from conventional medicine at the time.

• As lifespans increased in the 20th century, cases of senile dementia rose, sparking more interest. A major turning point came in 1976 when a researcher pointed out that Alzheimer’s disease could not be reliably distinguished from senile dementia based just on a patient’s age.

• Alzheimer’s disease and senile dementia are considered a single disease process rather than separate conditions. Classifying senile dementia as Alzheimer’s expanded the recognized number of Alzheimer’s cases.

• In 1984, researchers discovered that characteristic brain plaques found in Alzheimer’s are made of amyloid-β protein. Amyloid-β is a fragment produced when the APP protein is cut by enzymes. Mutations in genes coding for APP and thesecretase enzymes lead to early-onset Alzheimer’s.

• Genetics play an important role in both early- and late-onset Alzheimer’s. About 5% of cases are early-onset due to mutations in APP, PSEN1, or PSEN2. Late-onset Alzheimer’s has genetic links to many genes, like APOE, that increase risk rather than deterministically causing the disease.

• APOE ε4 variant strongly increases Alzheimer’s risk but is common since it may have conferred advantages earlier in life before symptoms appear. Genetic testing for risk variants could enable lifestyle changes to lower risk. Overall, Alzheimer’s like most diseases has a complex polygenic basis rather than being caused by single mutations.

• The baby’s parents were first cousins. Doctors sequenced the baby’s DNA after he began having seizures to try to diagnose the cause.

• The sequencing results came back in just 16 hours and identified a genetic condition called thiamine metabolism dysfunction syndrome 2.

• Doctors were then able to treat the baby with vitamin B1 solutions, which stopped the seizures. He recovered fully and was discharged the next day.

• Without genome sequencing, doctors would have had to trial different seizure medications without knowing the underlying cause. Earlier, the couple’s first child likely died from the same condition before a diagnosis was possible.

• Rapid whole genome sequencing is becoming an important tool for diagnosing genetic diseases in newborns and driving personalized treatment approaches. It has the potential to transform medicine.

• This discusses the origins and history of terms used for genetic disorders, like Down syndrome previously being called “mongolism.” The use of ethnic identifiers was problematic and eventually changed to clinical descriptions.

• Errors during fertilization can lead to chromosomal abnormalities, giving embryos an incorrect number of chromosomes. Having only one copy of an autosome is usually lethal early in pregnancy.

• Cri du chat syndrome is caused by a deletion on chromosome 5, missing the CTNND2 gene which is crucial for brain development. This causes intellectual disability.

• An extra autosomal chromosome is generally more lethal than an extra sex chromosome. Patau and Edward syndromes involve an extra chromosome 13 or 18 and are often fatal in the first year.

• Down syndrome involves an extra copy of chromosome 21, which has relatively few genes, making it somewhat tolerated. This leads to characteristic facial features and intellectual disabilities.

The key points are explanations of how chromosomal errors occur during fertilization and the effects of having an extra or missing chromosome, focusing on several genetic disorders as examples.

• Down syndrome occurs in about 1 in 300 pregnancies overall, but the risk increases significantly with maternal age, from less than 0.1% at age 20 to 10% at age 49. While 80% of Down syndrome cases occur in mothers under 35, many are unaware of the condition until birth.

• Dr. Jerome Lejeune discovered the genetic cause of Down syndrome in the late 1950s. However, this led to prenatal testing and more abortions when Down syndrome is detected, contrary to his hopes of finding a cure.

• Other chromosomal abnormalities that can occur include trisomies like Edwards syndrome and Patau syndrome. Screening tests are offered between 10-14 weeks of pregnancy to detect risk. Amniocentesis or chorionic villus sampling can confirm diagnosis. Most women choose abortion if abnormalities are found, as there is no cure currently.

• Complete or partial loss of chromosomes can also occur, typically involving the sex chromosomes X and Y. This can lead to conditions like Turner syndrome (missing X), Klinefelter syndrome (extra X), and others. Symptoms range from mild to severe.

• Implantation failure is actually the leading “cause of death” prior to birth, as over 50% of fertilized eggs fail to implant. Miscarriage rates are 10-20% of known pregnancies. Risk decreases after 12 weeks as major organs form.

• Specific causes of miscarriage are often unknown but can include chromosomal abnormalities, thyroid issues, diabetes, drug/alcohol use, smoking, uterine abnormalities, and rare immune issues.

• When functioning correctly, the immune system can recognize a pregnancy and suppress attacking the embryo. If the immune system is defective due to an autoimmune disorder, it may attack and cause recurrent miscarriage.

• Autoimmune disorders like multiple sclerosis, type 1 diabetes or Crohn’s disease can cause the immune system to attack the body’s healthy tissue. Lupus is another autoimmune disease linked to increased miscarriage rates.

• Healthy behaviors like eating well, avoiding smoking/alcohol, and managing conditions like diabetes can lower miscarriage risk. However, chromosomal abnormalities causing miscarriage generally cannot be controlled or repaired once a baby is born with them.

• The human capacity for violence dates back over 10,000 years, as evidenced by a Lake Turkana massacre site from this era showing remains of 27 people killed by weapons. Violence was commonly used to resolve conflicts both within and between early human groups.

• While hunter-gatherer lifeways necessitated cooperation, violence and accidental death were still common causes of mortality. Estimates suggest 16-25% of deaths in ancient societies and some modern foraging groups resulted from violence. Rules helped curb selfishness but broke down in large groups.

• Hammurabi’s code established a legal system in Babylon with standardized punishments for different crimes and social classes. For example, a doctor could charge more for treating a wealthy patient than a slave.

• Many punishments were fines, but the death penalty was also used. There was no imprisonment. Examples of laws included prohibitions on false accusations, theft, negligence causing flood damage, incest, assault causing injury.

• The code aimed to establish justice and protect the weak from the strong. It represented a move toward more transparent, consistent rules compared to previous arbitrary systems.

• The code focused on legal/criminal matters, not religious worship, in contrast to later biblical laws. Hobbes argued centralized states were necessary to avoid violent conflict and establish security through rule of law.

• Professional state armies enhanced state power by monopolizing violence. This led to greater internal peace and security within early agrarian empires like China and Rome hundreds of miles from borders.

• The Aztec state from 1345-1521 engaged in extensive warfare to conquer neighboring states and extract tribute. Warfare and human sacrifice were central to their culture.

• They would engage in “Flower Wars” arranged in advance with neighboring states to allow warriors to gain prestige by taking captives for sacrifice.

• The Aztecs sacrificed thousands of captives by cutting out their hearts on pyramids. Skull racks found at temples contained thousands of skulls.

• Even though 5% of the Aztec Empire’s citizens met a violent end, this was still lower than rates for hunter-gatherers. As states grew larger, the chances of being killed in battle fell greatly.

So in summary, the Aztec state had an extremely violent and warlike culture centered around human sacrifice, but even its high rates of violent death were surpassed by smaller hunter-gatherer societies, and statehood correlated with lower battlefield deaths as polities grew in size and scope.

• Chad Varah founded the Samaritans in the UK in 1953 to provide a listening ear for those struggling with emotional distress. He realized that volunteers were helping clients more than he could alone.

• The Samaritans now has over 20,000 volunteers across the UK and Ireland answering calls every six seconds. They listen confidentially and non-judgmentally to help provide hope and support.

• Similar organizations have spread internationally through Befrienders Worldwide in over 30 countries, saving many lives. Chad continued leading the London branch until 1974 and as president until 1986. He also did work helping with HIV/AIDS and stopping female genital mutilation.

• Due to the Samaritans’ anonymity, it’s hard to estimate how many lives Chad’s work saved over the years, but it is undoubtedly many thousands. He passed away in 2007 at age 95 after dedicating his life to helping others in need.

• Vodka originated from distilling fermented grains and became hugely popular in Russia, promoted by tsars who taxed its sale heavily. It was deeply ingrained in Russian culture by the 17th century.

• Under the Soviets, government policies varied from prohibition to promotion through taxation. Alcoholism increased life expectancy but also productivity.

• Gorbachev tried to curb alcoholism in the 1980s through restrictions and propaganda, but people switched to homemade alcohol and tax revenues fell. This contributed to his unpopularity.

• Yeltsin liberalized alcohol sales after the USSR fell, leading to high consumption rates. Genetic differences make some populations like East Asians more sensitive to alcohol.

• Evidence suggests humans evolved the ability to metabolize ethanol from fermented fruit 10 million years ago when early apes lived on the ground. Variations in alcohol dehydrogenase genes affect individuals’ reactions.

• Determining health effects of moderate alcohol is complex due to challenges of comparing groups that may differ in other ways like wealth. Careful epidemiological studies point to some benefits but also risks from excessive drinking.

• Moderate alcohol consumption (about 1 bottle of wine per week) may provide some health benefits like reducing risk of cardiovascular disease and diabetes. However, the optimal amount for health benefits is zero according to a comprehensive review.

• Excessive drinking can negatively impact health through increased risk of cancers, liver disease, cardiovascular problems, and more. It also increases risk of accidents and violence.

• Alcohol is addictive due to its effects on dopamine and reward circuits in the brain. Repeated use can lead to tolerance and cravings driven by environmental cues rather than pleasure.

• Many alcoholics use it to self-medicate emotional pain from trauma like childhood abuse or neglect. Traumatic early life experiences can permanently alter brain development and increase sensitivity to stress/addiction.

• Russia has high rates of alcoholism due to a history of state-sponsored alcohol promotion for tax revenue and the widespread childhood trauma of wars and famine in the 20th century, leaving many vulnerable to addiction.

• The discovery of the Americas by Christopher Columbus in 1492 had massive consequences for both continents. It initiated exchanges of plants, animals, diseases, people and more between Europe, Africa and the Americas, profoundly changing politics, religion, health and many other aspects of society.

• Native Americans were devastated by diseases brought from Europe like smallpox, measles and influenza, against which they had no immunity. It’s estimated around 90% of Native Americans died from these diseases.

• Europeans were given syphilis by Native Americans. It became a widespread epidemic in Europe until the 20th century.

• Tobacco was one of the crops exchanged in the Columbian exchange. Native Americans smoked and chewed tobacco leaves and Europeans were introduced to smoking tobacco on Columbus’ voyages. Though some saw it as satanic, it became popular in Europe.

• The English established permanent settlements in North America beginning in 1607 with the founding of Jamestown, Virginia by the Virginia Company, hoping to profit from potential gold or other treasures. Many early colonists wasted time searching for gold instead of setting up sustainable farms.

• The first winter at Jamestown colony was harsh and malaria infected many colonists. By the end of the first year, all but 38 of the original 144 colonists had died. An even worse winter in 1609-10 caused great starvation and loss of life.

• Jamestown struggled financially until tobacco was successfully cultivated. Tobacco grew well and became a profitable export crop, driving the growth of indentured servitude and later slavery as the workforce. This made Virginia a slave state and fueled the expansion of tobacco farming colonies.

• James Buchanan Duke revolutionized the cigarette industry in the late 1800s by partnering with an inventor to develop machines that could mass produce cigarettes, slashing costs. Duke then aggressively marketed cigarettes, contributing to their widespread popularity and public health issues later on.

• Tobacco companies like RJ Reynolds used sophisticated advertising and marketing techniques to brand and sell different cigarette types to diverse consumer groups. Cartoon characters like Joe Camel faced legal issues for targeting young people.

• Smoking became highly addictive as the nicotine delivery method refined over time, with cigarettes being the most efficient and popular means of using tobacco products by the 20th century. This had major public health consequences as the long-term health impacts of smoking became clear.

• Nicotine from cigarettes is rapidly absorbed into the bloodstream and transported to the brain within seconds. It binds to acetylcholine receptors, stimulating the release of neurotransmitters like dopamine that lead to pleasure and addiction.

• With continued smoking, tolerance develops as receptors become saturated. Smokers crave nicotine to avoid withdrawal symptoms like irritability and anxiety rather than for pleasure. Conditioning also reinforces addiction through environmental and behavioral cues associated with smoking.

• Genetic factors influence addiction risk. Enzymes like CYP2A6 that break down nicotine vary between people, affecting cravings and withdrawal. Slow metabolizers are less likely to get addicted.

• Cigarettes are highly engineered to be addictive. They provide a rapid hit of nicotine that fades quickly, conditioning repeated use. They are also cheap, legal, and suppress appetite. This makes quitting difficult.

• It took many decades to establish conclusively that smoking causes cancer and other diseases. Early studies by Doll and Bradford Hill in the 1940s-50s linked smoking to lung cancer through extensive epidemiological research. They showed smoking significantly increases cancer risks.

• Tobacco produces numerous mutagenic chemicals like benzopyrene that induce DNA mutations in oncogenes and tumor suppressor genes. This dysregulates cell growth and division, causing cancer over prolonged exposure through smoking.

The passage discusses how cigarette smoke contains numerous carcinogenic (cancer-causing) substances, including benzopyrene and toxic metals like lead, arsenic and cadmium. It explains that benzopyrene is known to cause lung cancer by mutating three critical guanines in the p53 gene, stopping p53 from working properly and thus turning lung cells cancerous.

It then provides a history of government and social efforts to curb smoking over the centuries through bans, restrictions, public health campaigns and litigation against tobacco companies. Anti-smoking policies have been shown to be effective over time in reducing cigarette consumption and subsequent rates of smoking-related diseases. However, completely banning or prohibiting smoking faces significant challenges and could create criminal black markets.

The tobacco industry has long sought to develop a “safe cigarette,” focusing research on lowering carcinogen delivery while retaining nicotine, but this is difficult due to the high temperatures produced during combustion. Modern vaping products may offer a less hazardous alternative to smoking, delivering nicotine at lower temperatures, but more research is still needed on their long-term health impacts. Some propose making tobacco sales illegal for future generations as a way to eventually phase out smoking altogether by 2100.

The passage discusses Ralph Nader’s book “Unsafe at Any Speed” which declared war on General Motors and brought attention to auto safety issues. Nader detailed many dangerous design flaws in cars that manufacturers were aware of but did not address, prioritizing style over safety. This included reflective and obscured lights, inconsistent gear patterns between cars, and poor quality control leading to defects. Nader’s book was initially difficult to publish but gained attention for its shocking claims. It helped spark increased federal regulation of auto safety standards to dramatically reduce traffic fatalities over the following decades.

• Ralph Nader’s 1965 book Unsafe at Any Speed criticized the auto industry for prioritizing profits over safety. It highlighted many unsafe design features like pointy ornamentation and lack of seatbelts that caused injuries and deaths.

• Auto executives were outraged. General Motors hired private investigators to spy on Nader, hoping to discredit him, but this backfired when it was uncovered in a Senate hearing. Sales of Nader’s book soared as a result.

• Nader’s work helped build public support for vehicle safety regulations. Congress passed the National Traffic and Motor Vehicle Safety Act of 1966, requiring safety standards. This led to mandatory features like seatbelts, padded dashboards, and improved design.

• In the decades since, continual safety improvements from airbags to collision avoidance technologies have dramatically reduced road deaths. Nader played a pivotal role in shifting the auto industry’s priorities towards preventing injuries over just addressing their consequences. His activism helped save many lives on the road.

• Unsafe at Any Speed by Ralph Nader was a hugely influential book that criticized the auto industry for producing dangerous cars. It helped spark legislation mandating greater car safety.

• New laws and government agencies inspired by Nader have prevented an estimated 3.5 million deaths in the 50 years since the book was published.

• Nader went on to found other consumer advocacy groups and ran for president multiple times. However, he is still disliked by some for his criticisms of corporations.

• Drunk driving laws began in the late 19th/early 20th century but were rarely enforced. Attitudes started to change after Candace Lightner founded Mothers Against Drunk Driving (MADD) in 1980 following the death of her daughter who was hit by a drunk driver.

• Working with politicians, MADD helped toughen drunk driving laws in the US, lower legal BAC limits, raise drinking ages, and increase penalties. This has reduced drunk driving deaths significantly since the 1980s though it remains a major cause of traffic fatalities.

• Overall traffic deaths have declined in the US since the 1970s due to safer vehicles, better laws, healthcare, and emergency response, even as driving has increased. But injuries from traffic remain a leading cause of death for young people.

Here is a summary of James Lind’s experiment with pairs of sailors testing various foods against scurvy:

• In 1747, James Lind conducted an early controlled experiment to test various treatments for scurvy aboard a British naval ship.

• He selected 12 men who all had scurvy and divided them into 6 pairs. Each pair was given a different dietary supplement to test for effectiveness against scurvy.

• The supplements given were: cider, vinegar, sulfuric acid, a plant elixir, seawater, and oranges and lemons.

• The only treatment that was effective was the pair given oranges and lemons, as they recovered quickly from scurvy while the other pairs saw little to no improvement.

• This was one of the first recorded controlled experiments and demonstrated that citrus fruits, with their vitamin C content, could prevent and cure scurvy, a major problem for sailors on long voyages.

• Lind’s work helped establish the concept of the controlled clinical trial to test medical treatments and played a key role in combating scurvy through the provision of lemon juice to sailors.

• Disease, cancer and hypertension were mentioned as common health issues. Two specific genes were highlighted - APOE and FOXO3. Variations in APOE are known to influence Alzheimer’s disease risk, while FOXO3 regulates many cellular processes important for healthspan.

• Studying centenarians’ DNA found SNPs that may delay age-related diseases, suggesting lifespan could be extended by introducing these changes.

• Regular monitoring of biological molecules in samples could detect health changes early, before symptoms appear. Devices could also track physiological data.

• Machine learning applied to these massive health datasets could identify disease patterns and predict onsets, enabling earlier intervention.

• 3D bioprinting and stem cell techniques may allow growing custom organs from a person’s own cells to replace failing organs, avoiding transplants. Organs could even be proactively replaced to maintain peak function.

• DNA editing of stem cells before organ growth could optimize function and eliminate genetic defects. This could significantly reduce mortality from organ failure.

The key ideas are ongoing development of advanced monitoring, machine learning applications, and regenerative medicine like organ biofabrication - which together could detect and treat disease much earlier to dramatically improve healthspans. Ethical issues will need addressing for clinical application.

Here is a summary of the key points from the data provided:

• Life expectancy steadily decreases with age, from over 90 years for newborns down to under 5 years for those aged 90 or over.

• Mortality rates are highest in the first year of life, then drop off sharply until age 55-57 for men and women respectively.

• The age with the lowest mortality is around 8 years old.

• Mortality rates then steadily increase with age, peaking around ages 85 for men and 89 for women.

• At age 54, a man has a life expectancy of 27.7 more years and a 0.4% chance of dying in the next year. His chances of living to 90 are 33%.

• Women generally have higher life expectancies than men at the same age. For example, a 54-year-old woman has a 50% greater chance of living to 90 than a man.

• About 6% of men die before age 54, compared to 4% of women.

• Overall the data provides information about mortality rates, life expectancies, and probabilities of death at different ages for the UK population.

Here is a summary of key points about the Black Death from the sources provided:

• The Black Death was a pandemic of bubonic plague in Eurasia in the 14th century that killed an estimated 30-60% of Europe’s population. It originated in Asia and spread along trade routes.

• Epidemics of plague had occurred in Europe for centuries prior, but the Black Death was particularly devastating due to increased globalization and trade. Rat fleas on trade ships likely spread Yersinia pestis bacteria.

• DNA evidence confirms Y. pestis as the causative agent. It was transmitted between humans via flea bites and respiratory droplets. Symptoms included buboes (swollen lymph nodes), fever, chills and vomiting of blood.

• Population decline due to the plague disrupted European societies and economies. It contributed to the demise of the Byzantine Empire and helped end the Medieval Warm Period. Recurring outbreaks continued for centuries.

• Lessons learned included the importance of sanitation, natural reservoirs of disease in rats/rodents, and the role of fleas in transmission. This led to improved public health measures like quarantines and plague hospitals.

• While debate remains on its extent in Asia and Africa, the Black Death had pandemics ramifications and represents a significant example of an epidemic disease outbreak in human history. Understanding its causes and consequences provides context for modern infectious disease threats.

This summarizes key papers related to the history of childbirth:

• Article discusses evolution of human bipedalism and challenges childbirth poses due to narrow pelvis. Horse foals can stand within an hour while human babies require intensive care.

• The Chamberlen family in the 1600s developed the earliest obstetric forceps but kept their use secret, possibly to profit from their midwifery practice.

• 19th century physician Charles Meigs documented the high mortality rates of puerperal (childbed) fever and argued it was contagious.

• Historian I. Loudon’s book discusses this disabling/fatal fever in new mothers and its impact.

• Paper outlines how the benefits of antisepsis to prevent puerperal fever were unknowingly demonstrated in the late 18th century by Dr. Alexander Gordon, although the causes were not understood at the time.

• Oliver Wendell Holmes’ 1843 essay argued puerperal fever was contagious and midwives/physicians spreading it between patients, a concept that was controversial but later accepted. Overall the papers examine the historical maternal health challenges of childbirth.

Here are summarizes of the sources provided:

1. New England Quarterly Journal of Medicine and Surgery, 1, 1842, 503–30. - This source appears to be a journal article from 1842 discussing medicine and surgery in New England. No other details are provided.

2. E.P. Hoyt, Improper Bostonian: Dr. Oliver Wendell Holmes, William Morrow & Co: New York, 1979. - This source is a book published in 1979 about Dr. Oliver Wendell Holmes, described as an “Improper Bostonian.”

3. I. Semmelweis, The Etiology, Concept, and Prophylaxis of Childbed Fever, 1861. - This source is a 1861 work by I. Semmelweis on the causes, concepts and prevention of childbed (puerperal) fever.

4. S. Halliday, The Great Filth: The War Against Disease in Victorian England, Sutton Publishing: Stroud, Gloucestershire, 2007. - This source is a book published in 2007 by S. Halliday about disease and efforts to combat it in Victorian England.

So in summary, the sources provided include a 19th century journal article, a 1979 biography, a 1861 medical text, and a 2007 history book. No other context is given about the content or arguments of the individual sources.

Here are summaries of references 003 and 108:

003: This reference outlines the history of lipid and protein analysis in the 19th century by scientists like Mulder, Liebig, and Gregory. They helped establish the chemical composition of foods and how nutrients are metabolized in the body.

108: This reference discusses a 2016 meta-analysis that found decreased bone mineral density is an independent risk factor for atherosclerosis. Having lower bone density increases the chances of developing atherosclerosis. It synthesizes evidence from multiple studies on this relationship between bone health and cardiovascular disease risk.

Here is a summary of the key sources provided:

• Article from Neanderthal exploration details recent discoveries about Neanderthals from the Italian government website.

• Several scientific articles discuss various aspects of human obesity like genetics, evolution, health risks, and treatments.

• One article provides an evolutionary perspective on human taste.

• Several sources discuss studying centenarians to better understand healthy aging and longevity, focusing on studies of Okinawan centenarians. This includes demographic data and importance of diet/lifestyle.

• Sources discuss DNA damage as a key factor in aging and calorie restriction extending lifespan in studies of yeast and humans.

• Reviews prescription medications used to treat overweight/obesity and results from a clinical trial of a once-weekly injectable medication for obesity.

• A biography of Woody Guthrie details his life and music career, including “This Land is Your Land.” Sources discuss the history of Huntington’s disease research and genetics.

• Sources provide context on an FLDS polygamist community in Utah and issues related to high rates of inbreeding depression. This includes data on recessive disease risks and impacts on sex ratios.

• Discuss hemophilia in the British royal family pedigree and the use of genetics to identify the remains of Tsar Nicholas II and his family.

• Details on Auguste D, the first patient diagnosed with Alzheimer’s disease, and the early history and debates around the disease.

• 7, 42, 327–49 = 278

• The passage discusses several studies related to Alzheimer’s disease and genetics.

• It mentions one study from 1976 that examined the prevalence and malignancy of Alzheimer’s disease.

• Another from 2007 discussed the pathogenesis of Alzheimer’s disease.

• A 1984 study reported on the purification and characterization of a novel cerebrovascular amyloid protein linked to Alzheimer’s.

• Additional references examined genetic factors like the CLU and APOE genes that influence Alzheimer’s risk.

• Overall the passage provides an overview of several seminal studies investigating the genetics and biological mechanisms underlying Alzheimer’s disease.

Here is a summary of the provided source:

The passage discusses Ralph Nader’s influential 1965 book “Unsafe at Any Speed” which criticized the U.S. auto industry, particularly General Motors, for producing vehicles with poor safety design. Nader showed how GM resisted including safety features like seat belts in order to keep costs down. The book fueled the consumer safety movement and directly led to the 1966 National Traffic and Motor Vehicle Safety Act which created new federal regulations for auto safety. The law tasked the National Highway Traffic Safety Administration with setting and enforcing design standards, resulting in major safety improvements to vehicles over subsequent decades. “Unsafe at Any Speed” is seen as having radically changed the relationship between consumers and manufacturers by putting safety concerns over profits.

Here is a summary of the key points from the sources provided on vehicle safety regulations:

• The National Traffic and Motor Vehicle Safety Act of 1966 was passed by Congress in response to rising concerns over traffic deaths in the US. It authorized the Department of Transportation to establish safety standards for motor vehicles.

• Early safety features on cars included things like windshield wipers, safety glass, seatbelts, airbags. Crash testing of vehicles has improved greatly over the decades.

• Ralph Nader’s influential 1965 book “Unsafe at Any Speed” was highly critical of the auto industry and lack of safety regulations. It is credited with helping spark stronger laws and oversight.

• Estimates suggest auto safety regulations have saved over 3.5 million lives in the US since 1966. Cars are statistically safer to drive now than ever before due to standards for things like crumple zones, anti-lock brakes, electronic stability control, etc.

• Mothers Against Drunk Driving (MADD) was formed in 1980 after the death of 13-year-old Cari Lightner at the hands of a drunk driver. It lobbied for stricter laws against drinking and driving.

• Car crashes remain a leading cause of death globally according to WHO statistics, emphasizing the ongoing need for policies and technologies to reduce traffic fatalities.

• Charles Dickens, diet, obesity, diphtheria, distillation, DNA sequencing, dogs, Richard Doll, dopamine, Down syndrome, drink-driving, drought, drug use, Duchenne muscular dystrophy, Duffy-negative gene, James Buchanan Duke, William Duncan, Dutch East India Company, Dutch Hunger Winter, Bob Dylan, dysentery, Pedro Ebeya, Ebola, Edward I of England, Edward II of England, Edward VII of England, Edward syndrome, Francis Egerton, Paul Ehrlich, Eiffel Tower, Eighty Years War, Christiaan Eijkman, Eleanor of Castile, elephantiasis, Elizabeth I of England, Elizabeth II of England, emphysema, English Civil War, ancient epidemics, epilepsy, Giles Everard, Flower Wars, football, forceps, Henry Ford, Four Horsemen of the Apocalypse, FOXO3 gene, Frälsegården, Frederick III of Germany, French Revolution

• Famines mentioned include the Great Famine of 1315, Irish Potato Famine, Bengal famine of 1943, Great Leap Forward in China, Ukraine 1932-33, North Korea, Ethiopia 1984-85, South Sudan 2013-2020

• Conditions mentioned include famine foods, William Farr, Fenland drainage, Ferdinand of Spain, fertility rates, Carlos Finlay, World War I, first-aiders, Bruce Frier, Theodor Frølich, fumarase deficiency, Fundamentalist LDS church, G6PD deficiency, Thomas Gainsborough, gallstones, Howard Gandelot, gene-drive technology, General Board of Health, genetic engineering, miasmatic theories, George Glenner, Global Hunger Index, Godin Tepe, Golden Gate Bridge, Golden Rice, Camillo Golgi, gonorrhoea

• Conditions continued: Mikhail Gorbachev, Alexander Gordon, William Gorgas, Giovanni Grassi, John Graunt, Great Fire of London, gross domestic product, Richard Grossman, guinea pigs, guinea-worm disease, Woody Guthrie, haemophilia, Hansel and Gretel, Sahachiro Hata, heart disease, hepatitis A and B, Hereditary Disease Foundation, Maurice Hilleman, Hillsborough disaster, Adolf Hitler, HIV/AIDS, Ho Chi Minh, Thomas Hobbes, Erich Hoffmann, Oliver Wendell Holmes, Axel Holst, Homer, homicide, Hong Kong, Hong Xiuquan, hookworm, Herbert Hoover, Alice Howland, hunter-gatherers, Huntington’s disease, Hutterian Brethren, hypertension

Here is a summary of the key terms from the list provided:

• schistosomiasis, schizophrenia, scurvy, Second World War, selective breeding, Semmelweis, Sen, Sender, Seven Years War, sewers, Shakespeare, Shunzhi, sickle-cell disease, Sierra Leone, Silk Roads, Simond, single-grain experiment, skeletons, slavery, sleep apnoea, sleeping sickness, smallpox, smoking, Snow, Soviet Union, Spanish–American War, Stalin, stroke, suicide, sulphonamides, sulphur dioxide, Sumeria, Sutton, syphilis, Tacitus, Taiping Rebellion, Takaki, Tarby, Ten Commandments, tetanus, thalassemia, thiamine metabolism dysfunction syndrome, Thirty Years War, thrifty gene hypothesis, thyroid gland, tobacco, tombstones, Townshend, TPOXX, Trafalgar, transplants, tuberculosis, Tull, typhoid, typhus, Ulpian’s table, Urban VII, US Centers for Disease Control and Prevention, US Food and Drug Administration, vaccination, Vietnam War, Vikings, Virginia, vitamins, volcanoes, walking upright, wash houses, Watson, Weber, weight-loss surgery, Weigl, Wexler, Whitehead, whooping cough, Wilhelm II, Wilkinson, William III, winemaking, witchcraft, Wong, Woodruff, World Health Organization, writing, yaws, Yeates, yellow fever, Yeltsin, Yersin, Young, zika, zinc

The list covered various diseases, historical events and figures, scientific discoveries and concepts, and organizations related to history of medicine and public health. Key recurring topics included diseases like smallpox, plague, influenza, historical periods like the Second World War, and scientists like Snow, Koch, Pasteur.