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Sunday, April 13, 2025

Preventive healthcare

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Preventive medicine physician
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  • Physician
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Medicine
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Education required
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Hospitals, clinics
Immunization against diseases is a key preventive healthcare measure.

Preventive healthcare, or prophylaxis, is the application of healthcare measures to prevent diseases. Disease and disability are affected by environmental factors, genetic predisposition, disease agents, and lifestyle choices, and are dynamic processes that begin before individuals realize they are affected. Disease prevention relies on anticipatory actions that can be categorized as primal,   primary, secondary, and tertiary prevention.

Each year, millions of people die of preventable causes. A 2004 study showed that about half of all deaths in the United States in 2000 were due to preventable behaviors and exposures. Leading causes included cardiovascular disease, chronic respiratory disease, unintentional injuries, diabetes, and certain infectious diseases. This same study estimates that 400,000 people die each year in the United States due to poor diet and a sedentary lifestyle. According to estimates made by the World Health Organization (WHO), about 55 million people died worldwide in 2011, and two-thirds of these died from non-communicable diseases, including cancer, diabetes, and chronic cardiovascular and lung diseases. This is an increase from the year 2000, during which 60% of deaths were attributed to these diseases.)

Preventive healthcare is especially important given the worldwide rise in the prevalence of chronic diseases and deaths from these diseases. There are many methods for prevention of disease. One of them is prevention of teenage smoking through information giving. It is recommended that adults and children aim to visit their doctor for regular check-ups, even if they feel healthy, to perform disease screening, identify risk factors for disease, discuss tips for a healthy and balanced lifestyle, stay up to date with immunizations and boosters, and maintain a good relationship with a healthcare provider. In pediatrics, some common examples of primary prevention are encouraging parents to turn down the temperature of their home water heater in order to avoid scalding burns, encouraging children to wear bicycle helmets, and suggesting that people use the air quality index (AQI) to check the level of pollution in the outside air before engaging in sporting activities. Some common disease screenings include checking for hypertension (high blood pressure), hyperglycemia (high blood sugar, a risk factor for diabetes mellitus), hypercholesterolemia (high blood cholesterol), screening for colon cancer, depression, HIV and other common types of sexually transmitted disease such as chlamydia, syphilis, and gonorrhea, mammography (to screen for breast cancer), colorectal cancer screening, a Pap test (to check for cervical cancer), and screening for osteoporosis. Genetic testing can also be performed to screen for mutations that cause genetic disorders or predisposition to certain diseases such as breast or ovarian cancer. However, these measures are not affordable for every individual and the cost effectiveness of preventive healthcare is still a topic of debate.

Overview

Preventive healthcare strategies are described as taking place at the primal, primary, secondary, and tertiary prevention levels. Although advocated as preventive medicine in the early twentieth century by Sara Josephine Baker, in the 1940s, Hugh R. Leavell and E. Gurney Clark coined the term primary prevention. They worked at the Harvard and Columbia University Schools of Public Health, respectively, and later expanded the levels to include secondary and tertiary prevention. Goldston (1987) notes that these levels might be better described as "prevention, treatment, and rehabilitation", although the terms primary, secondary, and tertiary prevention are still in use today. The concept of primal prevention has been created much more recently, in relation to the new developments in molecular biology over the last fifty years, more particularly in epigenetics, which point to the paramount importance of environmental conditions, both physical and affective, on the organism during its fetal and newborn life, or so-called primal period of life.

Level Definition
Primal and primordial prevention

Primal prevention has been propounded as a separate category of health promotion based on the evidence that epigenetic processes start at conception (see below: Primal and primordial preventions). Primordial prevention refers to measures designed to avoid the development of risk factors in the first place, early in life.

Primary prevention Methods to avoid occurrence of disease either through eliminating disease agents or increasing resistance to disease. Examples include immunization against disease, maintaining a healthy diet and exercise regimen, and avoiding smoking.
Secondary prevention Methods to detect and address an existing disease prior to the appearance of symptoms. Examples include treatment of hypertension (a risk factor for many cardiovascular diseases), and cancer screenings.
Tertiary prevention Methods to reduce the harm of symptomatic disease, such as disability or death, through rehabilitation and treatment. Examples include surgical procedures that halt the spread or progression of disease.
Quaternary prevention Methods to mitigate or avoid results of unnecessary or excessive interventions in the health system, including potential violations of rights.

Primal and primordial preventions

Primal prevention is health promotion par excellence. New knowledge in molecular biology, in particular epigenetics, points to how much affective as well as physical environment during fetal and newborn life may determine adult health. This way of promoting health consists mainly in providing future parents with pertinent, unbiased information on primal health and supporting them during their child's primal period of life (i.e., "from conception to first anniversary" according to definition by the Primal Health Research Centre, London). This includes adequate parental leave, ideally for both parents, with kin caregiving and financial help where needed.

Primordial prevention refers to all measures designed to prevent the development of risk factors in the first place, early in life, and even preconception, as Ruth A. Etzel has described it "all population-level actions and measures that inhibit the emergence and establishment of adverse environmental, economic, and social conditions". This could be reducing air pollution or prohibiting endocrine-disrupting chemicals in food-handling equipment and food contact materials.

Primary prevention

Primary prevention consists of traditional health promotion and "specific protection". Health promotion activities include prevention strategies such as health education and lifestyle medicine, and are current, non-clinical life choices such as eating nutritious meals and exercising often, that prevent lifestyle-related medical conditions, improve the quality of life, and create a sense of overall well-being. Preventing disease and creating overall well-being prolongs life expectancy. Health-promotional activities do not target a specific disease or condition but rather promote health and well-being on a very general level. On the other hand, specific protection targets a type or group of diseases and complements the goals of health promotion.

Food

Food is the most basic tool in preventive health care. Poor nutrition is linked to various chronic illnesses. Because of this, having a healthy diet and proper nutrition can be used to prevent illnesses.

Access

The 2011 National Health Interview Survey performed by the Centers for Disease Control was the first national survey to include questions about ability to pay for food. Difficulty with paying for food, medicine, or both is a problem facing 1 out of 3 Americans. If better food options were available through food banks, soup kitchens, and other resources for low-income people, obesity and the chronic conditions that come along with it would be better controlled. A food desert is an area with restricted access to healthy foods due to a lack of supermarkets within a reasonable distance. These are often low-income neighborhoods with the majority of residents lacking transportation. There have been several grassroots movements since 1995 to encourage urban gardening, using vacant lots to grow food cultivated by local residents. Mobile fresh markets are another resource for residents in a "food desert", which are specially outfitted buses bringing affordable fresh fruits and vegetables to low-income neighborhoods.

Food education and guidance

It has been proposed that healthy longevity diets are included in standard healthcare as switching from a "typical Western diet" could often extend life by a decade.

Protective measures

Specific protective measures such as water purification, sewage treatment, and the development of personal hygienic routines, such as regular hand-washing, safe sex to prevent sexually transmitted infections, became mainstream upon the discovery of infectious disease agents and have decreased the rates of communicable diseases which are spread in unsanitary conditions.

Scientific advancements in genetics have contributed to the knowledge of hereditary diseases and have facilitated progress in specific protective measures in individuals who are carriers of a disease gene or have an increased predisposition to a specific disease. Genetic testing has allowed physicians to make quicker and more accurate diagnoses and has allowed for tailored treatments or personalized medicine.

Food safety has a significant impact on human health and food quality monitoring has increased. Water, including drinking water, is also monitored in many cases for securing health. There also is some monitoring of air pollution. In many cases, environmental standards such as via maximum pollution levels, regulation of chemicals, occupational hygiene requirements or consumer protection regulations establish some protection in combination with the monitoring.

Preventive measures like vaccines and medical screenings are also important. Using PPE properly and getting the recommended vaccines and screenings can help decrease the spread of respiratory diseases, protecting the healthcare workers as well as their patients.

Secondary prevention

Secondary prevention deals with latent diseases and attempts to prevent an asymptomatic disease from progressing to symptomatic disease. Certain diseases can be classified as primary or secondary. This depends on definitions of what constitutes a disease, though, in general, primary prevention addresses the root cause of a disease or injury whereas secondary prevention aims to detect and treat a disease early on. Secondary prevention consists of "early diagnosis and prompt treatment" to contain the disease and prevent its spread to other individuals, and "disability limitation" to prevent potential future complications and disabilities from the disease. Early diagnosis and prompt treatment for a syphilis patient would include a course of antibiotics to destroy the pathogen and screening and treatment of any infants born to syphilitic mothers. Disability limitation for syphilitic patients includes continued check-ups on the heart, cerebrospinal fluid, and central nervous system of patients to curb any damaging effects such as blindness or paralysis.

Tertiary prevention

Finally, tertiary prevention attempts to reduce the damage caused by symptomatic disease by focusing on mental, physical, and social rehabilitation. Unlike secondary prevention, which aims to prevent disability, the objective of tertiary prevention is to maximize the remaining capabilities and functions of an already disabled patient. Goals of tertiary prevention include: preventing pain and damage, halting progression and complications from disease, and restoring the health and functions of the individuals affected by disease. For syphilitic patients, rehabilitation includes measures to prevent complete disability from the disease, such as implementing work-place adjustments for the blind and paralyzed or providing counseling to restore normal daily functions to the greatest extent possible.

The general use of machinery that has adequate ventilation and airflow is suggested for these patients in order to halt progression and complications of disease. A study conducted in nursing homes to prevent diseases concluded that the use of evaporative humidifiers to maintain the indoor humidity within the range 40–60% can reduce respiratory risk. Certain diseases thrive in different humidities, so the use of the humidifiers can help kill the particles of diseases.

Leading causes of preventable death

United States

The leading preventable cause of death in the United States is tobacco; however, poor diet and lack of exercise may soon surpass tobacco as a leading cause of death. These behaviors are modifiable and public health and prevention efforts could make a difference to reduce these deaths.

Leading causes of preventable deaths in the United States in 2000
Cause Deaths caused % of all deaths
Tobacco smoking 435,000 18.1
Poor diet and physical inactivity 400,000 16.6
Alcohol consumption 85,000 3.5
Infectious diseases 75,000 3.1
Toxicants 55,000 2.3
Traffic collisions 43,000 1.8
Firearm incidents 29,000 1.2
Sexually transmitted infections 20,000 0.8
Drug abuse 17,000 0.7

Worldwide

The leading causes of preventable death worldwide share similar trends to the United States. There are a few differences between the two, such as malnutrition, pollution, and unsafe sanitation, that reflect health disparities between the developing and developed world.

Leading causes of preventable death worldwide as of the year 2001
Cause Deaths caused (millions per year)
Hypertension 7.8
Smoking 5.0
High cholesterol 3.9
Malnutrition 3.8
Sexually transmitted infections 3.0
Poor diet 2.8
Overweight and obesity 2.5
Physical inactivity 2.0
Alcohol 1.9
Indoor air pollution from solid fuels 1.8
Unsafe water and poor sanitation 1.6

However, several of the leading causes of death – or underlying contributors to earlier death – may not be included as "preventable" causes of death. A study concluded that pollution was "responsible for approximately 9 million deaths per year" in 2019. And another study concluded that the global mean loss of life expectancy (a measure similar to years of potential life lost) from air pollution in 2015 was 2.9 years, substantially more than, for example, 0.3 years from all forms of direct violence, albeit a significant fraction of the LLE is considered to be unavoidable (such as pollution from some natural wildfires).

A landmark study conducted by the World Health Organization and the International Labour Organization found that exposure to long working hours is the occupational risk factor with the largest attributable burden of disease, i.e. an estimated 745,000 fatalities from ischemic heart disease and stroke events in 2016. With this study, prevention of exposure to long working hours has emerged as a priority for prevention healthcare in workplace settings.

Child mortality

In 2010, 7.6 million children died before reaching the age of 5. While this is a decrease from 9.6 million in 2000, it was still far from the fourth Millennium Development Goal to decrease child mortality by two-thirds by 2015. Of these deaths, about 64% were due to infection including diarrhea, pneumonia, and malaria. About 40% of these deaths occurred in neonates (children ages 1–28 days) due to pre-term birth complications. The highest number of child deaths occurred in Africa and Southeast Asia. As of 2015 in Africa, almost no progress has been made in reducing neonatal death since 1990. In 2010, India, Nigeria, Democratic Republic of the Congo, Pakistan, and China contributed to almost 50% of global child deaths. Targeting efforts in these countries is essential to reducing the global child death rate.

Child mortality is caused by factors including poverty, environmental hazards, and lack of maternal education. In 2003, the World Health Organization created a list of interventions in the following table that were judged economically and operationally "feasible," based on the healthcare resources and infrastructure in 42 nations that contribute to 90% of all infant and child deaths. The table indicates how many infant and child deaths could have been prevented in 2000, assuming universal healthcare coverage.

Leading preventive interventions as of 2003 reducing deaths in children 0–5 years old worldwide
Intervention Percent of all child deaths preventable
Breastfeeding 13
Insecticide-treated materials 7
Complementary feeding 6
Zinc 4
Clean delivery 4
Hib vaccine 4
Water, sanitation, hygiene 3
Antenatal steroids 3
Newborn temperature management 2
Vitamin A 2
Tetanus toxoid 2
Nevirapine and replacement feeding 2
Antibiotics for premature rupture of membranes 1
Measles vaccine 1
Antimalarial intermittent preventive treatment in pregnancy <1%

Preventive methods

Obesity

Obesity is a major risk factor for a wide variety of conditions including cardiovascular diseases, hypertension, certain cancers, and type 2 diabetes. In order to prevent obesity, it is recommended that individuals adhere to a consistent exercise regimen as well as a nutritious and balanced diet. A healthy individual should aim for acquiring 10% of their energy from proteins, 15-20% from fat, and over 50% from complex carbohydrates, while avoiding alcohol as well as foods high in fat, salt, and sugar. Sedentary adults should aim for at least half an hour of moderate-level daily physical activity and eventually increase to include at least 20 minutes of intense exercise, three times a week. Preventive health care offers many benefits to those that chose to participate in taking an active role in the culture. The medical system in our society is geared toward curing acute symptoms of disease after the fact that they have brought us into the emergency room. An ongoing epidemic within American culture is the prevalence of obesity. Healthy eating and regular exercise play a significant role in reducing an individual's risk for type 2 diabetes. A 2008 study concluded that about 23.6 million people in the United States had diabetes, including 5.7 million that had not been diagnosed. 90 to 95 percent of people with diabetes have type 2 diabetes. Diabetes is the main cause of kidney failure, limb amputation, and new-onset blindness in American adults.

Sexually transmitted infections

U.S. propaganda poster Fool the Axis Use Prophylaxis, 1942

Sexually transmitted infections (STIs), such as syphilis and HIV, are common but preventable with safe-sex practices. STIs can be asymptomatic, or cause a range of symptoms. Preventive measures for STIs are called prophylactics. The term especially applies to the use of condoms, which are highly effective at preventing disease, but also to other devices meant to prevent STIs, such as dental dams and latex gloves. Other means for preventing STIs include education on how to use condoms or other such barrier devices, testing partners before having unprotected sex, receiving regular STI screenings, to both receive treatment and prevent spreading STIs to partners, and, specifically for HIV, regularly taking prophylactic antiretroviral drugs, such as Truvada. Post-exposure prophylaxis, started within 72 hours (optimally less than 1 hour) after exposure to high-risk fluids, can also protect against HIV transmission.

Malaria prevention using genetic modification

Genetically modified mosquitoes are being used in developing countries to control malaria. This approach has been subject to objections and controversy.

Thrombosis

Thrombosis is a serious circulatory disease affecting thousands, usually older persons undergoing surgical procedures, women taking oral contraceptives and travelers. The consequences of thrombosis can be heart attacks and strokes. Prevention can include exercise, anti-embolism stockings, pneumatic devices, and pharmacological treatments.

Cancer

In recent years, cancer has become a global problem. Low and middle income countries share a majority of the cancer burden largely due to exposure to carcinogens resulting from industrialization and globalization. However, primary prevention of cancer and knowledge of cancer risk factors can reduce over one third of all cancer cases. Primary prevention of cancer can also prevent other diseases, both communicable and non-communicable, that share common risk factors with cancer.

Lung cancer

Distribution of lung cancer in the United States

Lung cancer is the leading cause of cancer-related deaths in the United States and Europe and is a major cause of death in other countries. Tobacco is an environmental carcinogen and the major underlying cause of lung cancer. Between 25% and 40% of all cancer deaths and about 90% of lung cancer cases are associated with tobacco use. Other carcinogens include asbestos and radioactive materials. Both smoking and second-hand exposure from other smokers can lead to lung cancer and eventually death.

Prevention of tobacco use is paramount to prevention of lung cancer. Individual, community, and statewide interventions can prevent or cease tobacco use. 90% of adults in the U.S. who have ever smoked did so prior to the age of 20. In-school prevention/educational programs, as well as counseling resources, can help prevent and cease adolescent smoking. Other cessation techniques include group support programs, nicotine replacement therapy (NRT), hypnosis, and self-motivated behavioral change. Studies have shown long term success rates (>1 year) of 20% for hypnosis and 10%-20% for group therapy.

Cancer screening programs serve as effective sources of secondary prevention. The Mayo Clinic, Johns Hopkins, and Memorial Sloan-Kettering hospitals conducted annual x-ray screenings and sputum cytology tests and found that lung cancer was detected at higher rates, earlier stages, and had more favorable treatment outcomes, which supports widespread investment in such programs.

Legislation can also affect smoking prevention and cessation. In 1992, Massachusetts (United States) voters passed a bill adding an extra 25 cent tax to each pack of cigarettes, despite intense lobbying and $7.3 million spent by the tobacco industry to oppose this bill. Tax revenue goes toward tobacco education and control programs and has led to a decline of tobacco use in the state.

Lung cancer and tobacco smoking are increasing worldwide, especially in China. China is responsible for about one-third of the global consumption and production of tobacco products. Tobacco control policies have been ineffective as China is home to 350 million regular smokers and 750 million passive smokers and the annual death toll is over 1 million. Recommended actions to reduce tobacco use include decreasing tobacco supply, increasing tobacco taxes, widespread educational campaigns, decreasing advertising from the tobacco industry, and increasing tobacco cessation support resources. In Wuhan, China, a 1998 school-based program implemented an anti-tobacco curriculum for adolescents and reduced the number of regular smokers, though it did not significantly decrease the number of adolescents who initiated smoking. This program was therefore effective in secondary but not primary prevention and shows that school-based programs have the potential to reduce tobacco use.

Skin cancer

An image of melanoma, one of the deadliest forms of skin cancer

Skin cancer is the most common cancer in the United States. The most lethal form of skin cancer, melanoma, leads to over 50,000 annual deaths in the United States. Childhood prevention is particularly important because a significant portion of ultraviolet radiation exposure from the sun occurs during childhood and adolescence and can subsequently lead to skin cancer in adulthood. Furthermore, childhood prevention can lead to the development of healthy habits that continue to prevent cancer for a lifetime.

The Centers for Disease Control and Prevention (CDC) recommends several primary prevention methods including: limiting sun exposure between 10 AM and 4 PM, when the sun is strongest, wearing tighter-weave natural cotton clothing, wide-brim hats, and sunglasses as protective covers, using sunscreens that protect against both UV-A and UV-B rays, and avoiding tanning salons. Sunscreen should be reapplied after sweating, exposure to water (through swimming for example) or after several hours of sun exposure. Since skin cancer is very preventable, the CDC recommends school-level prevention programs including preventive curricula, family involvement, participation and support from the school's health services, and partnership with community, state, and national agencies and organizations to keep children away from excessive UV radiation exposure.

Most skin cancer and sun protection data comes from Australia and the United States. An international study reported that Australians tended to demonstrate higher knowledge of sun protection and skin cancer knowledge, compared to other countries. Of children, adolescents, and adults, sunscreen was the most commonly used skin protection. However, many adolescents purposely used sunscreen with a low sun protection factor (SPF) in order to get a tan. Various Australian studies have shown that many adults failed to use sunscreen correctly; many applied sunscreen well after their initial sun exposure and/or failed to reapply when necessary. A 2002 case-control study in Brazil showed that only 3% of case participants and 11% of control participants used sunscreen with SPF >15.

Cervical cancer

The presence of cancer (adenocarcinoma) detected on a Pap test

Cervical cancer ranks among the top three most common cancers among women in Latin America, sub-Saharan Africa, and parts of Asia. Cervical cytology screening aims to detect abnormal lesions in the cervix so that women can undergo treatment prior to the development of cancer. Given that high quality screening and follow-up care has been shown to reduce cervical cancer rates by up to 80%, most developed countries now encourage sexually active women to undergo a Pap test every 3–5 years. Finland and Iceland have developed effective organized programs with routine monitoring and have managed to significantly reduce cervical cancer mortality while using fewer resources than unorganized, opportunistic programs such as those in the United States or Canada.

In developing nations in Latin America, such as Chile, Colombia, Costa Rica, and Cuba, both public and privately organized programs have offered women routine cytological screening since the 1970s. However, these efforts have not resulted in a significant change in cervical cancer incidence or mortality in these nations. This is likely due to low quality, inefficient testing. However, Puerto Rico, which has offered early screening since the 1960s, has witnessed almost a 50% decline in cervical cancer incidence and almost a four-fold decrease in mortality between 1950 and 1990. Brazil, Peru, India, and several high-risk nations in sub-Saharan Africa which lack organized screening programs, have a high incidence of cervical cancer.

Colorectal cancer

Colorectal cancer is globally the second most common cancer in women and the third-most common in men, and the fourth most common cause of cancer death after lung, stomach, and liver cancer, having caused 715,000 deaths in 2010.

It is also highly preventable; about 80 percent of colorectal cancers begin as benign growths, commonly called polyps, which can be easily detected and removed during a colonoscopy. Other methods of screening for polyps and cancers include fecal occult blood testing. Lifestyle changes that may reduce the risk of colorectal cancer include increasing consumption of whole grains, fruits and vegetables, and reducing consumption of red meat.

Dementia

The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response. Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP) which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed. Dementia can be prevented by reducing the risk factors for vascular disease such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk. A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk. In 2020, a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.

Health disparities and barriers to accessing care

Access to healthcare and preventive health services is unequal, as is the quality of care received. A study conducted by the Agency for Healthcare Research and Quality (AHRQ) revealed health disparities in the United States. In the United States, elderly adults (>65 years old) received worse care and had less access to care than their younger counterparts. The same trends are seen when comparing all racial minorities (black, Hispanic, Asian) to white patients, and low-income people to high-income people. Common barriers to accessing and utilizing healthcare resources included lack of income and education, language barriers, and lack of health insurance. Minorities were less likely than whites to possess health insurance, as were individuals who completed less education. These disparities made it more difficult for the disadvantaged groups to have regular access to a primary care provider, receive immunizations, or receive other types of medical care. Additionally, uninsured people tend to not seek care until their diseases progress to chronic and serious states and they are also more likely to forgo necessary tests, treatments, and filling prescription medications.

These sorts of disparities and barriers exist worldwide as well. Often, there are decades of gaps in life expectancy between developing and developed countries. For example, Japan has an average life expectancy that is 36 years greater than that in Malawi. Low-income countries also tend to have fewer physicians than high-income countries. In Nigeria and Myanmar, there are fewer than 4 physicians per 100,000 people while Norway and Switzerland have a ratio that is ten-fold higher. Common barriers worldwide include lack of availability of health services and healthcare providers in the region, great physical distance between the home and health service facilities, high transportation costs, high treatment costs, and social norms and stigma toward accessing certain health services.

Economics of lifestyle-based prevention

With lifestyle factors such as diet and exercise rising to the top of preventable death statistics, the economics of healthy lifestyle is a growing concern. There is little question that positive lifestyle choices provide an investment in health throughout life. To gauge success, traditional measures such as the quality years of life method (QALY), show great value. However, that method does not account for the cost of chronic conditions or future lost earnings because of poor health.

Developing future economic models that would guide both private and public investments as well as drive future policy to evaluate the efficacy of positive lifestyle choices on health is a major topic for economists globally. Americans spend over three trillion a year on health care but have a higher rate of infant mortality, shorter life expectancies, and a higher rate of diabetes than other high-income nations because of negative lifestyle choices. Despite these large costs, very little is spent on prevention for lifestyle-caused conditions in comparison. In 2016, the Journal of the American Medical Association estimated that $101 billion was spent in 2013 on the preventable disease of diabetes, and another $88 billion was spent on heart disease. In an effort to encourage healthy lifestyle choices, as of 2010 workplace wellness programs were on the rise but the economics and effectiveness data were continuing to evolve and develop.

Health insurance coverage impacts lifestyle choices, even intermittent loss of coverage had negative effects on healthy choices in the U.S. The repeal of the Affordable Care Act (ACA) could significantly impact coverage for many Americans as well as "The Prevention and Public Health Fund" which is the U.S. first and only mandatory funding stream dedicated to improving public health including counseling on lifestyle prevention issues, such as weight management, alcohol use, and treatment for depression.

Because in the U.S. chronic illnesses predominate as a cause of death and pathways for treating chronic illnesses are complex and multifaceted, prevention is a best practice approach to chronic disease when possible. In many cases, prevention requires mapping complex pathways to determine the ideal point for intervention. Cost-effectiveness of prevention is achievable, but impacted by the length of time it takes to see effects/outcomes of intervention. This makes prevention efforts difficult to fund—particularly in strained financial contexts. Prevention potentially creates other costs as well, due to extending the lifespan and thereby increasing opportunities for illness. In order to assess the cost-effectiveness of prevention, the cost of the preventive measure, savings from avoiding morbidity, and the cost from extending the lifespan need to be considered. Life extension costs become smaller when accounting for savings from postponing the last year of life, which makes up a large fraction of lifetime medical expenditures and becomes cheaper with age. Prevention leads to savings only if the cost of the preventive measure is less than the savings from avoiding morbidity net of the cost of extending the life span. In order to establish reliable economics of prevention for illnesses that are complicated in origin, knowing how best to assess prevention efforts, i.e. developing useful measures and appropriate scope, is required.

Effectiveness

There is no general consensus as to whether or not preventive healthcare measures are cost-effective, but they increase the quality of life dramatically. There are varying views on what constitutes a "good investment." Some argue that preventive health measures should save more money than they cost, when factoring in treatment costs in the absence of such measures. Others have argued in favor of "good value" or conferring significant health benefits even if the measures do not save money. Furthermore, preventive health services are often described as one entity though they comprise a myriad of different services, each of which can individually lead to net costs, savings, or neither. Greater differentiation of these services is necessary to fully understand both the financial and health effects.

A 2010 study reported that in the United States, vaccinating children, cessation of smoking, daily prophylactic use of aspirin, and screening of breast and colorectal cancers had the most potential to prevent premature death. Preventive health measures that resulted in savings included vaccinating children and adults, smoking cessation, daily use of aspirin, and screening for issues with alcoholism, obesity, and vision failure. These authors estimated that if usage of these services in the United States increased to 90% of the population, there would be net savings of $3.7 billion, which comprised only about -0.2% of the total 2006 United States healthcare expenditure. Despite the potential for decreasing healthcare spending, utilization of healthcare resources in the United States still remains low, especially among Latinos and African-Americans. Overall, preventive services are difficult to implement because healthcare providers have limited time with patients and must integrate a variety of preventive health measures from different sources.

While these specific services bring about small net savings, not every preventive health measure saves more than it costs. A 1970s study showed that preventing heart attacks by treating hypertension early on with drugs actually did not save money in the long run. The money saved by evading treatment from heart attack and stroke only amounted to about a quarter of the cost of the drugs. Similarly, it was found that the cost of drugs or dietary changes to decrease high blood cholesterol exceeded the cost of subsequent heart disease treatment. Due to these findings, some argue that rather than focusing healthcare reform efforts exclusively on preventive care, the interventions that bring about the highest level of health should be prioritized.

In 2008, Cohen et al. outlined a few arguments made by skeptics of preventive healthcare. Many argue that preventive measures only cost less than future treatment when the proportion of the population that would become ill in the absence of prevention is fairly large. The Diabetes Prevention Program Research Group conducted a 2012 study evaluating the costs and benefits in quality-adjusted life-years or QALYs of lifestyle changes versus taking the drug metformin. They found that neither method brought about financial savings, but were cost-effective nonetheless because they brought about an increase in QALYs. In addition to scrutinizing costs, preventive healthcare skeptics also examine efficiency of interventions. They argue that while many treatments of existing diseases involve use of advanced equipment and technology, in some cases, this is a more efficient use of resources than attempts to prevent the disease. Cohen suggested that the preventive measures most worth exploring and investing in are those that could benefit a large portion of the population to bring about cumulative and widespread health benefits at a reasonable cost.

Cost-effectiveness of childhood obesity interventions

There are at least four nationally implemented childhood obesity interventions in the United States: the Sugar-Sweetened Beverage excise tax (SSB), the TV AD program, active physical education (Active PE) policies, and early care and education (ECE) policies. They each have similar goals of reducing childhood obesity. The effects of these interventions on BMI have been studied, and the cost-effectiveness analysis (CEA) has led to a better understanding of projected cost reductions and improved health outcomes. The Childhood Obesity Intervention Cost-Effectiveness Study (CHOICES) was conducted to evaluate and compare the CEA of these four interventions.

Gortmaker, S.L. et al. (2015) states: "The four initial interventions were selected by the investigators to represent a broad range of nationally scalable strategies to reduce childhood obesity using a mix of both policy and programmatic strategies... 1. an excise tax of $0.01 per ounce of sweetened beverages, applied nationally and administered at the state level (SSB), 2. elimination of the tax deductibility of advertising costs of TV advertisements for "nutritionally poor" foods and beverages seen by children and adolescents (TV AD), 3. state policy requiring all public elementary schools in which physical education (PE) is currently provided to devote ≥50% of PE class time to moderate and vigorous physical activity (Active PE), and 4. state policy to make early child educational settings healthier by increasing physical activity, improving nutrition, and reducing screen time (ECE)." The CHOICES found that SSB, TV AD, and ECE led to net cost savings. Both SSB and TV AD increased quality adjusted life years and produced yearly tax revenue of 12.5 billion U.S. dollars and 80 million U.S. dollars, respectively.

Some challenges with evaluating the effectiveness of child obesity interventions include:

  1. The economic consequences of childhood obesity are both short and long term. In the short term, obesity impairs cognitive achievement and academic performance. Some believe this is secondary to negative effects on mood or energy, but others suggest there may be physiological factors involved. Furthermore, obese children have increased health care expenses (e.g. medications, acute care visits). In the long term, obese children tend to become obese adults with associated increased risk for a chronic condition such as diabetes or hypertension. Any effect on their cognitive development may also affect their contributions to society and socioeconomic status.
  2. In the CHOICES, it was noted that translating the effects of these interventions may in fact differ among communities throughout the nation. In addition it was suggested that limited outcomes are studied and these interventions may have an additional effect that is not fully appreciated.
  3. Modeling outcomes in such interventions in children over the long term is challenging because advances in medicine and medical technology are unpredictable. The projections from cost-effective analysis may need to be reassessed more frequently.

Economics of U.S. preventive care

As of 2009, the cost-effectiveness of preventive care is a highly debated topic. While some economists argue that preventive care is valuable and potentially cost saving, others believe it is an inefficient waste of resources. Preventive care is composed of a variety of clinical services and programs including annual doctor's check-ups, annual immunizations, and wellness programs; recent models show that these simple interventions can have significant economic impacts.

Clinical preventive services and programs

Research on preventive care addresses the question of whether it is cost saving or cost effective and whether there is an economics evidence base for health promotion and disease prevention. The need for and interest in preventive care is driven by the imperative to reduce health care costs while improving quality of care and the patient experience. Preventive care can lead to improved health outcomes and cost savings potential. Services such as health assessments/screenings, prenatal care, and telehealth and telemedicine can reduce morbidity or mortality with low cost or cost savings. Specifically, health assessments/screenings have cost savings potential, with varied cost-effectiveness based on screening and assessment type. Inadequate prenatal care can lead to an increased risk of prematurity, stillbirth, and infant death. Time is the ultimate resource and preventive care can help mitigate the time costs. Telehealth and telemedicine is one option that has gained consumer interest, acceptance, and confidence and can improve quality of care and patient satisfaction.

Economics for investment

There are benefits and trade-offs when considering investment in preventive care versus other types of clinical services. Preventive care can be a good investment as supported by the evidence base and can drive population health management objectives. The concepts of cost saving and cost-effectiveness are different and both are relevant to preventive care. Preventive care that may not save money may still provide health benefits; thus, there is a need to compare interventions relative to impact on health and cost.

Preventive care transcends demographics and is applicable to people of every age. The Health Capital Theory underpins the importance of preventive care across the lifecycle and provides a framework for understanding the variances in health and health care that are experienced. It treats health as a stock that provides direct utility. Health depreciates with age and the aging process can be countered through health investments. The theory further supports that individuals demand good health, that the demand for health investment is a derived demand (i.e. investment is health is due to the underlying demand for good health), and the efficiency of the health investment process increases with knowledge (i.e. it is assumed that the more educated are more efficient consumers and producers of health).

The prevalence elasticity of demand for prevention can also provide insights into the economics. Demand for preventive care can alter the prevalence rate of a given disease and further reduce or even reverse any further growth of prevalence. Reduction in prevalence subsequently leads to reduction in costs. There are a number of organizations and policy actions that are relevant when discussing the economics of preventive care services. The evidence base, viewpoints, and policy briefs from the Robert Wood Johnson Foundation, the Organisation for Economic Co-operation and Development (OECD), and efforts by the U.S. Preventive Services Task Force (USPSTF) all provide examples that improve the health and well-being of populations (e.g. preventive health assessments/screenings, prenatal care, and telehealth/telemedicine). The Affordable Care Act (ACA) has major influence on the provision of preventive care services, although it is currently under heavy scrutiny and review by the new administration. According to the Centers for Disease Control and Prevention (CDC), the ACA makes preventive care affordable and accessible through mandatory coverage of preventive services without a deductible, copayment, coinsurance, or other cost sharing.

The U.S. Preventive Services Task Force (USPSTF), a panel of national experts in prevention and evidence-based medicine, works to improve health of Americans by making evidence-based recommendations about clinical preventive services. They do not consider the cost of a preventive service when determining a recommendation. Each year, the organization delivers a report to Congress that identifies critical evidence gaps in research and recommends priority areas for further review.

The National Network of Perinatal Quality Collaboratives (NNPQC), sponsored by the CDC, supports state-based perinatal quality collaboratives (PQCs) in measuring and improving upon health care and health outcomes for mothers and babies. These PQCs have contributed to improvements such as reduction in deliveries before 39 weeks, reductions in healthcare associated bloodstream infections, and improvements in the utilization of antenatal corticosteroids.

Telehealth and telemedicine has realized significant growth and development recently. The Center for Connected Health Policy (The National Telehealth Policy Resource Center) has produced multiple reports and policy briefs on the topic of Telehealth and Telemedicine and how they contribute to preventive services. Policy actions and provision of preventive services do not guarantee utilization. Reimbursement has remained a significant barrier to adoption due to variances in payer and state level reimbursement policies and guidelines through government and commercial payers. Americans use preventive services at about half the recommended rate and cost-sharing, such as deductibles, co-insurance, or copayments, also reduce the likelihood that preventive services will be used. Despite the ACA's enhancement of Medicare benefits and preventive services, there were no effects on preventive service utilization, calling out the fact that other fundamental barriers exist.

Affordable Care Act and preventive healthcare

The Patient Protection and Affordable Care Act, also known as just the Affordable Care Act or Obamacare, was passed and became law in the United States on March 23, 2010. The finalized and newly ratified law was to address many issues in the U.S. healthcare system, which included expansion of coverage, insurance market reforms, better quality, and the forecast of efficiency and costs. Under the insurance market reforms the act required that insurance companies no longer exclude people with pre-existing conditions, allow for children to be covered on their parents' plan until the age of 26, and expand appeals that dealt with reimbursement denials. The Affordable Care Act also banned the limited coverage imposed by health insurances, and insurance companies were to include coverage for preventive health care services. The U.S. Preventive Services Task Force has categorized and rated preventive health services as either A or B, as to which insurance companies must comply and present full coverage. Not only has the U.S. Preventive Services Task Force provided graded preventive health services that are appropriate for coverage, they have also provided many recommendations to clinicians and insurers to promote better preventive care to ultimately provide better quality of care and lower the burden of costs.

Health insurance

Healthcare insurance companies are willing to pay for preventive care despite the fact that patients are not acutely sick in hope that it will prevent them from developing a chronic disease later on in life. Today, health insurance plans offered through the Marketplace, mandated by the Affordable Care Act are required to provide certain preventive care services free of charge to patients. Section 2713 of the Affordable Care Act, specifies that all private Marketplace and all employer-sponsored private plans (except those grandfathered in) are required to cover preventive care services that are ranked A or B by the U.S. Preventive Services Task Force free of charge to patients. UnitedHealthcare insurance company has published patient guidelines at the beginning of the year explaining their preventive care coverage.

Evaluating incremental benefits

Evaluating the incremental benefits of preventive care requires a longer period of time when compared to acutely ill patients. Inputs into the model such as discounting rate and time horizon can have significant effects on the results. One controversial subject is use of a 10-year time frame to assess cost effectiveness of diabetes preventive services by the Congressional Budget Office.

Preventive care services mainly focus on chronic disease. The Congressional Budget Office has provided guidance that further research is needed in the area of the economic impacts of obesity in the U.S. before the CBO can estimate budgetary consequences. A bipartisan report published in May 2015 recognizes the potential of preventive care to improve patients' health at individual and population levels while decreasing the healthcare expenditure.

Economic case

Mortality from modifiable risk factors

Chronic diseases such as heart disease, stroke, diabetes, obesity and cancer have become the most common and costly health problems in the United States. In 2014, it was projected that by 2023 that the number of chronic disease cases would increase by 42%, resulting in $4.2 trillion in treatment and lost economic output. They are also among the top ten leading causes of mortality. Chronic diseases are driven by risk factors that are largely preventable. Sub-analysis performed on all deaths in the United States in 2000 revealed that almost half were attributed to preventable behaviors including tobacco, poor diet, physical inactivity and alcohol consumption. More recent analysis reveals that heart disease and cancer alone accounted for nearly 46% of all deaths. Modifiable risk factors are also responsible for a large morbidity burden, resulting in poor quality of life in the present and loss of future life earning years. It is further estimated that by 2023, focused efforts on the prevention and treatment of chronic disease may result in 40 million fewer chronic disease cases, potentially reducing treatment costs by $220 billion.

Childhood vaccinations

Childhood immunizations are largely responsible for the increase in life expectancy in the 20th century. From an economic standpoint, childhood vaccines demonstrate a very high return on investment. According to Healthy People 2020, for every birth cohort that receives the routine childhood vaccination schedule, direct health care costs are reduced by $9.9 billion and society saves $33.4 billion in indirect costs. The economic benefits of childhood vaccination extend beyond individual patients to insurance plans and vaccine manufacturers, all while improving the health of the population.

Health capital theory

The burden of preventable illness extends beyond the healthcare sector, incurring costs related to lost productivity among workers in the workforce. Indirect costs related to poor health behaviors and associated chronic disease costs U.S. employers billions of dollars each year.

According to the American Diabetes Association (ADA), medical costs for employees with diabetes are twice as high as for workers without diabetes and are caused by work-related absenteeism ($5 billion), reduced productivity at work ($20.8 billion), inability to work due to illness-related disability ($21.6 billion), and premature mortality ($18.5 billion). Reported estimates of the cost burden due to increasingly high levels of overweight and obese members in the workforce vary, with best estimates suggesting 450 million more missed work days, resulting in $153 billion each year in lost productivity, according to the CDC Healthy Workforce.

The health capital model explains how individual investments in health can increase earnings by "increasing the number of healthy days available to work and to earn income." In this context, health can be treated both as a consumption good, wherein individuals desire health because it improves quality of life in the present, and as an investment good because of its potential to increase attendance and workplace productivity over time. Preventive health behaviors such as healthful diet, regular exercise, access to and use of well-care, avoiding tobacco, and limiting alcohol can be viewed as health inputs that result in both a healthier workforce and substantial cost savings.

Quality-adjusted life years

Health benefits of preventive care measures can be described in terms of quality-adjusted life-years (QALYs) saved. A QALY takes into account length and quality of life, and is used to evaluate the cost-effectiveness of medical and preventive interventions. Classically, one year of perfect health is defined as 1 QALY and a year with any degree of less than perfect health is assigned a value between 0 and 1 QALY. As an economic weighting system, the QALY can be used to inform personal decisions, to evaluate preventive interventions and to set priorities for future preventive efforts.

Cost-saving and cost-effective benefits of preventive care measures are well established. The Robert Wood Johnson Foundation evaluated the prevention cost-effectiveness literature, and found that many preventive measures meet the benchmark of <$100,000 per QALY and are considered to be favorably cost-effective. These include screenings for HIV and chlamydia, cancers of the colon, breast and cervix, vision screening, and screening for abdominal aortic aneurysms in men >60 in certain populations. Alcohol and tobacco screening were found to be cost-saving in some reviews and cost-effective in others. According to the RWJF analysis, two preventive interventions were found to save costs in all reviews: childhood immunizations and counseling adults on the use of aspirin.

Minority populations

Health disparities are increasing in the United States for chronic diseases such as obesity, diabetes, cancer, and cardiovascular disease. Populations at heightened risk for health inequities are the growing proportion of racial and ethnic minorities, including African Americans, American Indians, Hispanics/Latinos, Asian Americans, Alaska Natives and Pacific Islanders.

According to the Racial and Ethnic Approaches to Community Health (REACH), a national CDC program, non-Hispanic blacks currently have the highest rates of obesity (48%), and risk of newly diagnosed diabetes is 77% higher among non-Hispanic blacks, 66% higher among Hispanics/Latinos and 18% higher among Asian Americans compared to non-Hispanic whites. Current U.S. population projections predict that more than half of Americans will belong to a minority group by 2044. Without targeted preventive interventions, medical costs from chronic disease inequities will become unsustainable. Broadening health policies designed to improve delivery of preventive services for minority populations may help reduce substantial medical costs caused by inequities in health care, resulting in a return on investment.

Policies

Chronic disease is a population level issue that requires population health level efforts and national and state level public policy to effectively prevent, rather than individual level efforts. The United States currently employs many public health policy efforts aligned with the preventive health efforts discussed above. The Centers for Disease Control and Prevention support initiatives such as Health in All Policies and HI-5 (Health Impact in 5 Years), and collaborative efforts that aim to consider prevention across sectors and address social determinants of health as a method of primary prevention for chronic disease.

Obesity

Policies that address the obesity epidemic should be proactive and far-reaching, including a variety of stakeholders both in healthcare and in other sectors. Recommendations from the Institute of Medicine in 2012 suggest that "concerted action be taken across and within five environments (physical activity (PA), food and beverage, marketing and messaging, healthcare and worksites, and schools) and all sectors of society (including government, business and industry, schools, child care, urban planning, recreation, transportation, media, public health, agriculture, communities, and home) in order for obesity prevention efforts to truly be successful."

There are dozens of current policies acting at either (or all of) the federal, state, local and school levels. Most states employ a physical education requirement of 150 minutes of physical education per week at school, a policy of the National Association of Sport and Physical Education. In some cities, including Philadelphia, a sugary food tax is employed. This is a part of an amendment to Title 19 of the Philadelphia Code, "Finance, Taxes and Collections", Chapter 19-4100, Sugar-Sweetened Beverage Tax that was approved 2016, which establishes an excise tax of $0.015 per fluid ounce on distributors of beverages sweetened with both caloric and non-caloric sweeteners. Distributors are required to file a return with the department, and the department can collect taxes, among other responsibilities. These policies can be a source of tax credits. Under the Philadelphia policy, businesses can apply for tax credits with the revenue department on a first-come, first-served basis. This applies until the total amount of credits for a particular year reaches one million dollars.

Recently, advertisements for food and beverages directed at children have received much attention. The Children's Food and Beverage Advertising Initiative (CFBAI) is a self-regulatory program of the food industry. Each participating company makes a public pledge that details its commitment to advertise only foods that meet certain nutritional criteria to children under 12 years old. This is a self-regulated program with policies written by the Council of Better Business Bureaus. The Robert Wood Johnson Foundation funded research to test the efficacy of the CFBAI. The results showed progress in terms of decreased advertising of food products that target children and adolescents.

Childhood immunization policies

Despite nationwide controversies over childhood vaccination and immunization, there are policies and programs at the federal, state, local and school levels outlining vaccination requirements. All states require children to be vaccinated against certain communicable diseases as a condition for school attendance. However, only 18 states allow exemptions for "philosophical or moral reasons." Diseases for which vaccinations form part of the standard ACIP vaccination schedule are diphtheria tetanus pertussis (whooping cough), poliomyelitis (polio), measles, mumps, rubella, haemophilus influenzae type b, hepatitis B, influenza, and pneumococcal infections. The CDC website maintains such schedules.

The CDC website describes a federally funded program, Vaccines for Children (VFC), which provides vaccines at no cost to children who might not otherwise be vaccinated because of inability to pay. Additionally, the Advisory Committee on Immunization Practices (ACIP) is an expert vaccination advisory board that informs vaccination policy and guides on-going recommendations to the CDC, incorporating the most up-to-date cost-effectiveness and risk-benefit evidence in its recommendations.

DNA glycosylase

From Wikipedia, the free encyclopedia

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

Glycosylases were first discovered in bacteria, and have since been found in all kingdoms of life. In addition to their role in base excision repair, DNA glycosylase enzymes have been implicated in the repression of gene silencing in A. thaliana, N. tabacum and other plants by active demethylation. 5-methylcytosine residues are excised and replaced with unmethylated cytosines allowing access to the chromatin structure of the enzymes and proteins necessary for transcription and subsequent translation.

Monofunctional vs. bifunctional glycosylases

There are two main classes of glycosylases: monofunctional and bifunctional. Monofunctional glycosylases have only glycosylase activity, whereas bifunctional glycosylases also possess AP lyase activity that permits them to cut the phosphodiester bond of DNA, creating a single-strand break without the need for an AP endonuclease. β-Elimination of an AP site by a glycosylase-lyase yields a 3' α,β-unsaturated aldehyde adjacent to a 5' phosphate, which differs from the AP endonuclease cleavage product. Some glycosylase-lyases can further perform δ-elimination, which converts the 3' aldehyde to a 3' phosphate.

Biochemical mechanism

The first crystal structure of a DNA glycosylase was obtained for E. coli Nth. This structure revealed that the enzyme flips the damaged base out of the double helix into an active site pocket in order to excise it. Other glycosylases have since been found to follow the same general paradigm, including human UNG pictured below. To cleave the N-glycosidic bond, monofunctional glycosylases use an activated water molecule to attack carbon 1 of the substrate. Bifunctional glycosylases, instead, use an amine residue as a nucleophile to attack the same carbon, going through a Schiff base intermediate.

Types of glycosylases

Crystal structures of many glycosylases have been solved. Based on structural similarity, glycosylases are grouped into four superfamilies. The UDG and AAG families contain small, compact glycosylases, whereas the MutM/Fpg and HhH-GPD families comprise larger enzymes with multiple domains.

A wide variety of glycosylases have evolved to recognize different damaged bases. The table below summarizes the properties of known glycosylases in commonly studied model organisms.

Glycosylases in bacteria, yeast and humans
E. coli B. cereus Yeast (S. cerevisiae) Human Type Substrates
AlkA AlkE Mag1 MPG (N-methylpurine DNA glycosylase) monofunctional 3-meA(3-alkyladenine), hypoxanthine
UDG
Ung1 UNG monofunctional uracil
Fpg
Ogg1 hOGG1 bifunctional 8-oxoG (8-Oxoguanine), FapyG
Nth
Ntg1 hNTH1 bifunctional Tg, hoU, hoC, urea, FapyG(2,6-diamino-4-hydroxy-5-formamidopyrimidine)
Ntg2
Nei
Not present hNEIL1 bifunctional Tg, hoU, hoC, urea, FapyG, FapyA(4,6-diamino-5-formamidopyrimidine)
hNEIL2 AP site, hoU
hNEIL3 unknown
MutY
Not present hMYH monofunctional A:8-oxoG
Not present
Not present hSMUG1 monofunctional U, hoU(5-hydroxyuracil), hmU(5-hydroxymethyluracil), fU(5-formyluracil)
Not present
Not present TDG monofunctional T:G mispair
Not present
Not present MBD4 monofunctional T:G mispair
AlkC AlkC Not present Not present monofunctional Alkylpurine
AlkD AlkD Not present Not present monofunctional Alkylpurine

DNA glycosylases can be grouped into the following categories based on their substrate(s):

Uracil DNA glycosylases

Structure of the base-excision repair enzyme uracil-DNA glycosylase. The uracil residue is shown in yellow.

In molecular biology, the protein family, Uracil-DNA glycosylase (UDG) is an enzyme that reverts mutations in DNA. The most common mutation is the deamination of cytosine to uracil. UDG repairs these mutations. UDG is crucial in DNA repair, without it these mutations may lead to cancer.

This entry represents various uracil-DNA glycosylases and related DNA glycosylases (EC), such as uracil-DNA glycosylase, thermophilic uracil-DNA glycosylase, G:T/U mismatch-specific DNA glycosylase (Mug), and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1).

Uracil DNA glycosylases remove uracil from DNA, which can arise either by spontaneous deamination of cytosine or by the misincorporation of dU opposite dA during DNA replication. The prototypical member of this family is E. coli UDG, which was among the first glycosylases discovered. Four different uracil-DNA glycosylase activities have been identified in mammalian cells, including UNG, SMUG1, TDG, and MBD4. They vary in substrate specificity and subcellular localization. SMUG1 prefers single-stranded DNA as substrate, but also removes U from double-stranded DNA. In addition to unmodified uracil, SMUG1 can excise 5-hydroxyuracil, 5-hydroxymethyluracil and 5-formyluracil bearing an oxidized group at ring C5. TDG and MBD4 are strictly specific for double-stranded DNA. TDG can remove thymine glycol when present opposite guanine, as well as derivatives of U with modifications at carbon 5. Current evidence suggests that, in human cells, TDG and SMUG1 are the major enzymes responsible for the repair of the U:G mispairs caused by spontaneous cytosine deamination, whereas uracil arising in DNA through dU misincorporation is mainly dealt with by UNG. MBD4 is thought to correct T:G mismatches that arise from deamination of 5-methylcytosine to thymine in CpG sites. MBD4 mutant mice develop normally and do not show increased cancer susceptibility or reduced survival. But they acquire more C T mutations at CpG sequences in epithelial cells of the small intestine.

The structure of human UNG in complex with DNA revealed that, like other glycosylases, it flips the target nucleotide out of the double helix and into the active site pocket. UDG undergoes a conformational change from an ‘‘open’’ unbound state to a ‘‘closed’’ DNA-bound state.

UDG
Epstein–Barr virus uracil-dna glycosylase in complex with ugi from pbs-2
Identifiers
SymbolUDG
PfamPF03167
InterProIPR005122
PROSITEPDOC00121
SCOP21udg / SCOPe / SUPFAM
CDDcd09593

Available protein structures:

History

Lindahl was the first to observe repair of uracil in DNA. UDG was purified from Escherichia coli, and this hydrolysed the N-glycosidic bond connecting the base to the deoxyribose sugar of the DNA backbone.

Function

The function of UDG is to remove mutations in DNA, more specifically removing uracil.

Structure

These proteins have a 3-layer alpha/beta/alpha structure. The polypeptide topology of UDG is that of a classic alpha/beta protein. The structure consists primarily of a central, four-stranded, all parallel beta sheet surrounded on either side by a total of eight alpha helices and is termed a parallel doubly wound beta sheet.

Mechanism

Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosydic bond, initiating the base excision repair pathway. Uracil in DNA can arise either through the deamination of cytosine to form mutagenic U:G mispairs, or through the incorporation of dUMP by DNA polymerase to form U:A pairs. These aberrant uracil residues are genotoxic.

Localisation

In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human UNG1 protein is transported to both the mitochondria and the nucleus.

Conservation

The sequence of uracil-DNA glycosylase is extremely well conserved in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localization, but the presence of a mitochondrial transit peptide has not been directly demonstrated. The most N-terminal conserved region contains an aspartic acid residue which has been proposed, based on X-ray structures to act as a general base in the catalytic mechanism.

Family

There are two UDG families, named Family 1 and Family 2. Family 1 is active against uracil in ssDNA and dsDNA. Family 2 excise uracil from mismatches with guanine.

Glycosylases of oxidized bases

8-oxoG (syn) in a Hoogsteen base pair with dA (anti)

A variety of glycosylases have evolved to recognize oxidized bases, which are commonly formed by reactive oxygen species generated during cellular metabolism. The most abundant lesions formed at guanine residues are 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 8-oxoguanine. Due to mispairing with adenine during replication, 8-oxoG is highly mutagenic, resulting in G to T transversions. Repair of this lesion is initiated by the bifunctional DNA glycosylase OGG1, which recognizes 8-oxoG paired with C. hOGG1 is a bifunctional glycosylase that belongs to the helix-hairpin-helix (HhH) family. MYH recognizes adenine mispaired with 8-oxoG but excises the A, leaving the 8-oxoG intact. OGG1 knockout mice do not show an increased tumor incidence, but accumulate 8-oxoG in the liver as they age. A similar phenotype is observed with the inactivation of MYH, but simultaneous inactivation of both MYH and OGG1 causes 8-oxoG accumulation in multiple tissues including lung and small intestine. In humans, mutations in MYH are associated with increased risk of developing colon polyps and colon cancer. In addition to OGG1 and MYH, human cells contain three additional DNA glycosylases, NEIL1, NEIL2, and NEIL3. These are homologous to bacterial Nei, and their presence likely explains the mild phenotypes of the OGG1 and MYH knockout mice.

Glycosylases of alkylated bases

This group includes E. coli AlkA and related proteins in higher eukaryotes. These glycosylases are monofunctional and recognize methylated bases, such as 3-methyladenine.

AlkA

AlkA refers to 3-methyladenine DNA glycosylase II.

Pathology

Epigenetic deficiencies in cancers

Epigenetic alterations (epimutations) in DNA glycosylase genes have only recently begun to be evaluated in a few cancers, compared to the numerous previous studies of epimutations in genes acting in other DNA repair pathways (such as MLH1 in mismatch repair and MGMT in direct reversal). Two examples of epimutations in DNA glycosylase genes that occur in cancers are summarized below.

Hydrolysis of cytosine to uracil

MBD4 (methyl-CpG-binding domain protein 4) is a glycosylase employed in an initial step of base excision repair. MBD4 protein binds preferentially to fully methylated CpG sites. These altered bases arise from the frequent hydrolysis of cytosine to uracil (see image) and hydrolysis of 5-methylcytosine to thymine, producing G:U and G:T base pairs. If the improper uracils or thymines in these base pairs are not removed before DNA replication, they will cause transition mutations. MBD4 specifically catalyzes the removal of T and U paired with guanine (G) within CpG sites. This is an important repair function since about 1/3 of all intragenic single base pair mutations in human cancers occur in CpG dinucleotides and are the result of G:C to A:T transitions. These transitions comprise the most frequent mutations in human cancer. For example, nearly 50% of somatic mutations of the tumor suppressor gene p53 in colorectal cancer are G:C to A:T transitions within CpG sites. Thus, a decrease in expression of MBD4 could cause an increase in carcinogenic mutations.

MBD4 expression is reduced in almost all colorectal neoplasms due to methylation of the promoter region of MBD4. Also MBD4 is deficient due to mutation in about 4% of colorectal cancers,

A majority of histologically normal fields surrounding neoplastic growths (adenomas and colon cancers) in the colon also show reduced MBD4 mRNA expression (a field defect) compared to histologically normal tissue from individuals who never had a colonic neoplasm. This finding suggests that epigenetic silencing of MBD4 is an early step in colorectal carcinogenesis.

In a Chinese population that was evaluated, the MBD4 Glu346Lys polymorphism was associated with about a 50% reduced risk of cervical cancer, suggesting that alterations in MBD4 is important in this cancer.

NEIL1

Nei-like (NEIL) 1 is a DNA glycosylase of the Nei family (which also contains NEIL2 and NEIL3).[35] NEIL1 is a component of the DNA replication complex needed for surveillance of oxidized bases before replication, and appears to act as a “cowcatcher” to slow replication until NEIL1 can act as a glycosylase and remove the oxidatively damaged base.

NEIL1 protein recognizes (targets) and removes certain oxidatively-damaged bases and then incises the abasic site via β,δ elimination, leaving 3′ and 5′ phosphate ends. NEIL1 recognizes oxidized pyrimidines, formamidopyrimidines, thymine residues oxidized at the methyl group, and both stereoisomers of thymine glycol. The best substrates for human NEIL1 appear to be the hydantoin lesions, guanidinohydantoin, and spiroiminodihydantoin that are further oxidation products of 8-oxoG. NEIL1 is also capable of removing lesions from single-stranded DNA as well as from bubble and forked DNA structures. A deficiency in NEIL1 causes increased mutagenesis at the site of an 8-oxo-Gua:C pair, with most mutations being G:C to T:A transversions.

A study in 2004 found that 46% of primary gastric cancers had reduced expression of NEIL1 mRNA, though the mechanism of reduction was not known. This study also found that 4% of gastric cancers had mutations in the NEIL1 gene. The authors suggested that low NEIL1 activity arising from reduced expression and/or mutation of the NEIL1 gene was often involved in gastric carcinogenesis.

A screen of 145 DNA repair genes for aberrant promoter methylation was performed on head and neck squamous cell carcinoma (HNSCC) tissues from 20 patients and from head and neck mucosa samples from 5 non-cancer patients. This screen showed that the NEIL1 gene had substantially increased hypermethylation, and of the 145 DNA repair genes evaluated, NEIL1 had the most significantly different frequency of methylation. Furthermore, the hypermethylation corresponded to a decrease in NEIL1 mRNA expression. Further work with 135 tumor and 38 normal tissues also showed that 71% of HNSCC tissue samples had elevated NEIL1 promoter methylation.

When 8 DNA repair genes were evaluated in non-small cell lung cancer (NSCLC) tumors, 42% were hypermethylated in the NEIL1 promoter region. This was the most frequent DNA repair abnormality found among the 8 DNA repair genes tested. NEIL1 was also one of six DNA repair genes found to be hypermethylated in their promoter regions in colorectal cancer.

Saturday, April 12, 2025

Naturalism (philosophy)

From Wikipedia, the free encyclopedia
Double rainbow at Yosemite National Park. According to naturalism, the causes of all phenomena are to be found within the universe and not transcendental factors beyond it.

In philosophy, naturalism is the idea that only natural laws and forces (as opposed to supernatural ones) operate in the universe. In its primary sense, it is also known as ontological naturalism, metaphysical naturalism, pure naturalism, philosophical naturalism and antisupernaturalism. "Ontological" refers to ontology, the philosophical study of what exists. Philosophers often treat naturalism as equivalent to materialism, but there are important distinctions between the philosophies.

For example, philosopher Paul Kurtz argued that nature is best accounted for by reference to material principles. These principles include mass, energy, and other physical and chemical properties accepted by the scientific community. Further, this sense of naturalism holds that spirits, deities, and ghosts are not real and that there is no "purpose" in nature. This stronger formulation of naturalism is commonly referred to as metaphysical naturalism. On the other hand, the more moderate view that naturalism should be assumed in one's working methods as the current paradigm, without any further consideration of whether naturalism is true in the robust metaphysical sense, is called methodological naturalism.

With the exception of pantheists – who believe that nature is identical with divinity while not recognizing a distinct personal anthropomorphic god – theists challenge the idea that nature contains all of reality. According to some theists, natural laws may be viewed as secondary causes of God(s).

In the 20th century, Willard Van Orman Quine, George Santayana, and other philosophers argued that the success of naturalism in science meant that scientific methods should also be used in philosophy. According to this view, science and philosophy are not always distinct from one another, but instead form a continuum.

"Naturalism is not so much a special system as a point of view or tendency common to a number of philosophical and religious systems; not so much a well-defined set of positive and negative doctrines as an attitude or spirit pervading and influencing many doctrines. As the name implies, this tendency consists essentially in looking upon nature as the one original and fundamental source of all that exists, and in attempting to explain everything in terms of nature. Either the limits of nature are also the limits of existing reality, or at least the first cause, if its existence is found necessary, has nothing to do with the working of natural agencies. All events, therefore, find their adequate explanation within nature itself. But, as the terms nature and natural are themselves used in more than one sense, the term naturalism is also far from having one fixed meaning".

History

Ancient and medieval philosophy

Naturalism is most notably a Western phenomenon, but an equivalent idea has long existed in the East. Naturalism was the foundation of two out of six orthodox schools and one heterodox school of Hinduism. Samkhya, one of the oldest schools of Indian philosophy puts nature (Prakriti) as the primary cause of the universe, without assuming the existence of a personal God or Ishvara. The Carvaka, Nyaya, Vaisheshika schools originated in the 7th, 6th, and 2nd century BCE, respectively. Similarly, though unnamed and never articulated into a coherent system, one tradition within Confucian philosophy embraced a form of Naturalism dating to the Wang Chong in the 1st century, if not earlier, but it arose independently and had little influence on the development of modern naturalist philosophy or on Eastern or Western culture.

Ancient Roman mosaic showing Anaximander holding a sundial. One of the contributors to naturalism in ancient Greek philosophy

Western metaphysical naturalism originated in ancient Greek philosophy. The earliest pre-Socratic philosophers, especially the Milesians (Thales, Anaximander, and Anaximenes) and the atomists (Leucippus and Democritus), were labeled by their peers and successors "the physikoi" (from the Greek φυσικός or physikos, meaning "natural philosopher" borrowing on the word φύσις or physis, meaning "nature") because they investigated natural causes, often excluding any role for gods in the creation or operation of the world. This eventually led to fully developed systems such as Epicureanism, which sought to explain everything that exists as the product of atoms falling and swerving in a void.

Aristotle surveyed the thought of his predecessors and conceived of nature in a way that charted a middle course between their excesses.

Plato's world of eternal and unchanging Forms, imperfectly represented in matter by a divine Artisan, contrasts sharply with the various mechanistic Weltanschauungen, of which atomism was, by the fourth century at least, the most prominent This debate was to persist throughout the ancient world. Atomistic mechanism got a shot in the arm from Epicurus while the Stoics adopted a divine teleology The choice seems simple: either show how a structured, regular world could arise out of undirected processes, or inject intelligence into the system. This was how Aristotle… when still a young acolyte of Plato, saw matters. Cicero… preserves Aristotle's own cave-image: if troglodytes were brought on a sudden into the upper world, they would immediately suppose it to have been intelligently arranged. But Aristotle grew to abandon this view; although he believes in a divine being, the Prime Mover is not the efficient cause of action in the Universe, and plays no part in constructing or arranging it But, although he rejects the divine Artificer, Aristotle does not resort to a pure mechanism of random forces. Instead he seeks to find a middle way between the two positions, one which relies heavily on the notion of Nature, or phusis.

With the rise and dominance of Christianity in the West and the later spread of Islam, metaphysical naturalism was generally abandoned by intellectuals. Thus, there is little evidence for it in medieval philosophy.

Modern philosophy

It was not until the early modern era of philosophy and the Age of Enlightenment that naturalists like Benedict Spinoza (who put forward a theory of psychophysical parallelism), David Hume, and the proponents of French materialism (notably Denis Diderot, Julien La Mettrie, and Baron d'Holbach) started to emerge again in the 17th and 18th centuries. In this period, some metaphysical naturalists adhered to a distinct doctrine, materialism, which became the dominant category of metaphysical naturalism widely defended until the end of the 19th century.

Thomas Hobbes was a proponent of naturalism in ethics who acknowledged normative truths and properties. Immanuel Kant rejected (reductionist) materialist positions in metaphysics, but he was not hostile to naturalism. His transcendental philosophy is considered to be a form of liberal naturalism.

Hegel who together with Joseph von Schelling developed the form of natural philosophy recognised as Naturphilosophie

In late modern philosophy, Naturphilosophie, a form of natural philosophy, was developed by Friedrich Wilhelm Joseph von Schelling and Georg Wilhelm Friedrich Hegel as an attempt to comprehend nature in its totality and to outline its general theoretical structure.

A version of naturalism that arose after Hegel was Ludwig Feuerbach's anthropological materialism, which influenced Karl Marx and Friedrich Engels's historical materialism, Engels's "materialist dialectic" philosophy of nature (Dialectics of Nature), and their follower Georgi Plekhanov's dialectical materialism.

Another notable school of late modern philosophy advocating naturalism was German materialism: members included Ludwig Büchner, Jacob Moleschott, and Carl Vogt.

The current usage of the term naturalism "derives from debates in America in the first half of the 20th century. The self-proclaimed 'naturalists' from that period included John Dewey, Ernest Nagel, Sidney Hook, and Roy Wood Sellars."

Contemporary philosophy

A politicized version of naturalism that has arisen in contemporary philosophy is Ayn Rand's Objectivism. Objectivism is an expression of capitalist ethical idealism within a naturalistic framework. An example of a more progressive naturalistic philosophy is secular humanism.

The current usage of the term naturalism derives from debates in America in the first half of the last century.

Currently, metaphysical naturalism is more widely embraced than in previous centuries, especially but not exclusively in the natural sciences and the Anglo-American, analytic philosophical communities. While the vast majority of the population of the world remains firmly committed to non-naturalistic worldviews, contemporary defenders of naturalism and/or naturalistic theses and doctrines today include Graham Oppy, Kai Nielsen, J. J. C. Smart, David Malet Armstrong, David Papineau, Paul Kurtz, Brian Leiter, Daniel Dennett, Michael Devitt, Fred Dretske, Paul and Patricia Churchland, Mario Bunge, Jonathan Schaffer, Hilary Kornblith, Leonard Olson, Quentin Smith, Paul Draper and Michael Martin, among many other academic philosophers.

According to David Papineau, contemporary naturalism is a consequence of the build-up of scientific evidence during the twentieth century for the "causal closure of the physical", the doctrine that all physical effects can be accounted for by physical causes.

By the middle of the twentieth century, the acceptance of the causal closure of the physical realm led to even stronger naturalist views. The causal closure thesis implies that any mental and biological causes must themselves be physically constituted, if they are to produce physical effects. It thus gives rise to a particularly strong form of ontological naturalism, namely the physicalist doctrine that any state that has physical effects must itself be physical. From the 1950s onwards, philosophers began to formulate arguments for ontological physicalism. Some of these arguments appealed explicitly to the causal closure of the physical realm (Feigl 1958, Oppenheim and Putnam 1958). In other cases, the reliance on causal closure lay below the surface. However, it is not hard to see that even in these latter cases the causal closure thesis played a crucial role.

In contemporary continental philosophy, Quentin Meillassoux proposed speculative materialism, a post-Kantian return to David Hume which can strengthen classical materialist ideas. This speculative approach to philosophical naturalism has been further developed by other contemporary thinkers including Ray Brassier and Drew M. Dalton.

Etymology

The term "methodological naturalism" is much more recent, though. According to Ronald Numbers, it was coined in 1983 by Paul de Vries, a Wheaton College philosopher. De Vries distinguished between what he called "methodological naturalism", a disciplinary method that says nothing about God's existence, and "metaphysical naturalism", which "denies the existence of a transcendent God". The term "methodological naturalism" had been used in 1937 by Edgar S. Brightman in an article in The Philosophical Review as a contrast to "naturalism" in general, but there the idea was not really developed to its more recent distinctions.

Description

Flammarion engraving A 21st century image of the universe and a 1888 illustration of the cosmos.

According to Steven Schafersman, naturalism is a philosophy that maintains that;

  1. "Nature encompasses all that exists throughout space and time;
  2. Nature (the universe or cosmos) consists only of natural elements, that is, of spatio-temporal physical substance – massenergy. Non-physical or quasi-physical substance, such as information, ideas, values, logic, mathematics, intellect, and other emergent phenomena, either supervene upon the physical or can be reduced to a physical account;
  3. Nature operates by the laws of physics and in principle, can be explained and understood by science and philosophy;
  4. The supernatural does not exist, i.e., only nature is real. Naturalism is therefore a metaphysical philosophy opposed primarily by supernaturalism".

Or, as Carl Sagan succinctly put it: "The Cosmos is all that is or ever was or ever will be."

In addition Arthur C. Danto states that naturalism, in recent usage, is a species of philosophical monism according to which whatever exists or happens is natural in the sense of being susceptible to explanation through methods which, although paradigmatically exemplified in the natural sciences, are continuous from domain to domain of objects and events. Hence, naturalism is polemically defined as repudiating the view that there exists or could exist any entities which lie, in principle, beyond the scope of scientific explanation.

Arthur Newell Strahler states: "The naturalistic view is that the particular universe we observe came into existence and has operated through all time and in all its parts without the impetus or guidance of any supernatural agency." "The great majority of contemporary philosophers urge that that reality is exhausted by nature, containing nothing 'supernatural', and that the scientific method should be used to investigate all areas of reality, including the 'human spirit'." Philosophers widely regard naturalism as a "positive" term, and "few active philosophers nowadays are happy to announce themselves as 'non-naturalists'". "Philosophers concerned with religion tend to be less enthusiastic about 'naturalism'" and that despite an "inevitable" divergence due to its popularity, if more narrowly construed, (to the chagrin of John McDowell, David Chalmers and Jennifer Hornsby, for example), those not so disqualified remain nonetheless content "to set the bar for 'naturalism' higher."

Alvin Plantinga stated that Naturalism is presumed to not be a religion. However, in one very important respect it resembles religion by performing the cognitive function of a religion. There is a set of deep human questions to which a religion typically provides an answer. In like manner naturalism gives a set of answers to these questions".

Providing assumptions required for science

According to Robert Priddy, all scientific study inescapably builds on at least some essential assumptions that cannot be tested by scientific processes; that is, that scientists must start with some assumptions as to the ultimate analysis of the facts with which it deals. These assumptions would then be justified partly by their adherence to the types of occurrence of which we are directly conscious, and partly by their success in representing the observed facts with a certain generality, devoid of ad hoc suppositions." Kuhn also claims that all science is based on assumptions about the character of the universe, rather than merely on empirical facts. These assumptions – a paradigm – comprise a collection of beliefs, values and techniques that are held by a given scientific community, which legitimize their systems and set the limitations to their investigation. For naturalists, nature is the only reality, the "correct" paradigm, and there is no such thing as supernatural, i.e. anything above, beyond, or outside of nature. The scientific method is to be used to investigate all reality, including the human spirit.

Some claim that naturalism is the implicit philosophy of working scientists, and that the following basic assumptions are needed to justify the scientific method:

  1. That there is an objective reality shared by all rational observers. "The basis for rationality is acceptance of an external objective reality." "Objective reality is clearly an essential thing if we are to develop a meaningful perspective of the world. Nevertheless its very existence is assumed." "Our belief that objective reality exist is an assumption that it arises from a real world outside of ourselves. As infants we made this assumption unconsciously. People are happy to make this assumption that adds meaning to our sensations and feelings, than live with solipsism." "Without this assumption, there would be only the thoughts and images in our own mind (which would be the only existing mind) and there would be no need of science, or anything else."
  2. That this objective reality is governed by natural laws;
    "Science, at least today, assumes that the universe obeys knowable principles that don't depend on time or place, nor on subjective parameters such as what we think, know or how we behave." Hugh Gauch argues that science presupposes that "the physical world is orderly and comprehensible."
  3. That reality can be discovered by means of systematic observation and experimentation.
    Stanley Sobottka said: "The assumption of external reality is necessary for science to function and to flourish. For the most part, science is the discovering and explaining of the external world." "Science attempts to produce knowledge that is as universal and objective as possible within the realm of human understanding."
  4. That Nature has uniformity of laws and most if not all things in nature must have at least a natural cause.
    Biologist Stephen Jay Gould referred to these two closely related propositions as the constancy of nature's laws and the operation of known processes. Simpson agrees that the axiom of uniformity of law, an unprovable postulate, is necessary in order for scientists to extrapolate inductive inference into the unobservable past in order to meaningfully study it. "The assumption of spatial and temporal invariance of natural laws is by no means unique to geology since it amounts to a warrant for inductive inference which, as Bacon showed nearly four hundred years ago, is the basic mode of reasoning in empirical science. Without assuming this spatial and temporal invariance, we have no basis for extrapolating from the known to the unknown and, therefore, no way of reaching general conclusions from a finite number of observations. (Since the assumption is itself vindicated by induction, it can in no way "prove" the validity of induction — an endeavor virtually abandoned after Hume demonstrated its futility two centuries ago)." Gould also notes that natural processes such as Lyell's "uniformity of process" are an assumption: "As such, it is another a priori assumption shared by all scientists and not a statement about the empirical world." According to R. Hooykaas: "The principle of uniformity is not a law, not a rule established after comparison of facts, but a principle, preceding the observation of facts ... It is the logical principle of parsimony of causes and of economy of scientific notions. By explaining past changes by analogy with present phenomena, a limit is set to conjecture, for there is only one way in which two things are equal, but there are an infinity of ways in which they could be supposed different."
  5. That experimental procedures will be done satisfactorily without any deliberate or unintentional mistakes that will influence the results.
  6. That experimenters won't be significantly biased by their presumptions.
  7. That random sampling is representative of the entire population.
    A simple random sample (SRS) is the most basic probabilistic option used for creating a sample from a population. The benefit of SRS is that the investigator is guaranteed to choose a sample that represents the population that ensures statistically valid conclusions.

Methodological naturalism

Aristotle, one of the philosophers behind the modern day scientific method used as a central term in methodological naturalism

Methodological naturalism, the second sense of the term "naturalism", (see above) is "the adoption or assumption of philosophical naturalism … with or without fully accepting or believing it.” Robert T. Pennock used the term to clarify that the scientific method confines itself to natural explanations without assuming the existence or non-existence of the supernatural. "We may therefore be agnostic about the ultimate truth of [philosophical] naturalism, but nevertheless adopt it and investigate nature as if nature is all that there is."

According to Ronald Numbers, the term "methodological naturalism" was coined in 1983 by Paul de Vries, a Wheaton College philosopher.

Both Schafersman and Strahler assert that it is illogical to try to decouple the two senses of naturalism. "While science as a process only requires methodological naturalism, the practice or adoption of methodological naturalism entails a logical and moral belief in philosophical naturalism, so they are not logically decoupled." This “[philosophical] naturalistic view is espoused by science as its fundamental assumption."

But Eugenie Scott finds it imperative to do so for the expediency of deprogramming the religious. "Scientists can defuse some of the opposition to evolution by first recognizing that the vast majority of Americans are believers, and that most Americans want to retain their faith." Scott apparently believes that "individuals can retain religious beliefs and still accept evolution through methodological naturalism. Scientists should therefore avoid mentioning metaphysical naturalism and use methodological naturalism instead." "Even someone who may disagree with my logic … often understands the strategic reasons for separating methodological from philosophical naturalism—if we want more Americans to understand evolution."

Scott’s approach has found success as illustrated in Ecklund’s study where some religious scientists reported that their religious beliefs affect the way they think about the implications – often moral – of their work, but not the way they practice science within methodological naturalism. Papineau notes that "Philosophers concerned with religion tend to be less enthusiastic about metaphysical naturalism and that those not so disqualified remain content "to set the bar for 'naturalism' higher."

In contrast to Schafersman, Strahler, and Scott, Robert T. Pennock, an expert witness at the Kitzmiller v. Dover Area School District trial and cited by the Judge in his Memorandum Opinion. described "methodological naturalism" stating that it is not based on dogmatic metaphysical naturalism.

Pennock further states that as supernatural agents and powers "are above and beyond the natural world and its agents and powers" and "are not constrained by natural laws", only logical impossibilities constrain what a supernatural agent cannot do. In addition he says: "If we could apply natural knowledge to understand supernatural powers, then, by definition, they would not be supernatural." "Because the supernatural is necessarily a mystery to us, it can provide no grounds on which one can judge scientific models." "Experimentation requires observation and control of the variables.... But by definition we have no control over supernatural entities or forces."

The position that the study of the function of nature is also the study of the origin of nature is in contrast with opponents who take the position that functioning of the cosmos is unrelated to how it originated. While they are open to supernatural fiat in its invention and coming into existence, during scientific study to explain the functioning of the cosmos, they do not appeal to the supernatural. They agree that allowing "science to appeal to untestable supernatural powers to explain how nature functions would make the scientist's task meaningless, undermine the discipline that allows science to make progress, and would be as profoundly unsatisfying as the ancient Greek playwright's reliance upon the deus ex machina to extract his hero from a difficult predicament."

Views on methodological naturalism

W. V. O. Quine

W. V. O. Quine describes naturalism as the position that there is no higher tribunal for truth than natural science itself. In his view, there is no better method than the scientific method for judging the claims of science, and there is neither any need nor any place for a "first philosophy", such as (abstract) metaphysics or epistemology, that could stand behind and justify science or the scientific method.

Therefore, philosophy should feel free to make use of the findings of scientists in its own pursuit, while also feeling free to offer criticism when those claims are ungrounded, confused, or inconsistent. In Quine's view, philosophy is "continuous with" science, and both are empirical. Naturalism is not a dogmatic belief that the modern view of science is entirely correct. Instead, it simply holds that science is the best way to explore the processes of the universe and that those processes are what modern science is striving to understand.

Karl Popper

Karl Popper equated naturalism with inductive theory of science. He rejected it based on his general critique of induction (see problem of induction), yet acknowledged its utility as means for inventing conjectures.

A naturalistic methodology (sometimes called an "inductive theory of science") has its value, no doubt. I reject the naturalistic view: It is uncritical. Its upholders fail to notice that whenever they believe to have discovered a fact, they have only proposed a convention. Hence the convention is liable to turn into a dogma. This criticism of the naturalistic view applies not only to its criterion of meaning, but also to its idea of science, and consequently to its idea of empirical method.

— Karl R. Popper, The Logic of Scientific Discovery, (Routledge, 2002), pp. 52–53, ISBN 0-415-27844-9.

Popper instead proposed that science should adopt a methodology based on falsifiability for demarcation, because no number of experiments can ever prove a theory, but a single experiment can contradict one. Popper holds that scientific theories are characterized by falsifiability.

Alvin Plantinga

Alvin Plantinga, Professor Emeritus of Philosophy at Notre Dame, and a Christian, has become a well-known critic of naturalism. He suggests, in his evolutionary argument against naturalism, that the probability that evolution has produced humans with reliable true beliefs, is low or inscrutable, unless the evolution of humans was guided (for example, by God). According to David Kahan of the University of Glasgow, in order to understand how beliefs are warranted, a justification must be found in the context of supernatural theism, as in Plantinga's epistemology. (See also supernormal stimuli).

Plantinga argues that together, naturalism and evolution provide an insurmountable "defeater for the belief that our cognitive faculties are reliable", i.e., a skeptical argument along the lines of Descartes' evil demon or brain in a vat.

Take philosophical naturalism to be the belief that there aren't any supernatural entities – no such person as God, for example, but also no other supernatural entities, and nothing at all like God. My claim was that naturalism and contemporary evolutionary theory are at serious odds with one another – and this despite the fact that the latter is ordinarily thought to be one of the main pillars supporting the edifice of the former. (Of course I am not attacking the theory of evolution, or anything in that neighborhood; I am instead attacking the conjunction of naturalism with the view that human beings have evolved in that way. I see no similar problems with the conjunction of theism and the idea that human beings have evolved in the way contemporary evolutionary science suggests.) More particularly, I argued that the conjunction of naturalism with the belief that we human beings have evolved in conformity with current evolutionary doctrine is in a certain interesting way self-defeating or self-referentially incoherent.

— Alvin Plantinga, Naturalism Defeated?: Essays on Plantinga's Evolutionary Argument Against Naturalism, "Introduction"

The argument is controversial and has been criticized as seriously flawed, for example, by Elliott Sober.

Robert T. Pennock

Robert T. Pennock states that as supernatural agents and powers "are above and beyond the natural world and its agents and powers" and "are not constrained by natural laws", only logical impossibilities constrain what a supernatural agent cannot do. He says: "If we could apply natural knowledge to understand supernatural powers, then, by definition, they would not be supernatural." As the supernatural is necessarily a mystery to us, it can provide no grounds on which one can judge scientific models. "Experimentation requires observation and control of the variables.... But by definition we have no control over supernatural entities or forces." Science does not deal with meanings; the closed system of scientific reasoning cannot be used to define itself. Allowing science to appeal to untestable supernatural powers would make the scientist's task meaningless, undermine the discipline that allows science to make progress, and "would be as profoundly unsatisfying as the ancient Greek playwright's reliance upon the deus ex machina to extract his hero from a difficult predicament."

Naturalism of this sort says nothing about the existence or nonexistence of the supernatural, which by this definition is beyond natural testing. As a practical consideration, the rejection of supernatural explanations would merely be pragmatic, thus it would nonetheless be possible for an ontological supernaturalist to espouse and practice methodological naturalism. For example, scientists may believe in God while practicing methodological naturalism in their scientific work. This position does not preclude knowledge that is somehow connected to the supernatural. Generally however, anything that one can examine and explain scientifically would not be supernatural, simply by definition.

Human extinction

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