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Monday, June 5, 2023

Starvation

From Wikipedia, the free encyclopedia
Starvation
Girl affected by famine in Buguruslan, Russia - 1921.jpg
Starving Russian girl during the Russian famine of 1921–1922
SpecialtyCritical care medicine
Symptomsfeeling weak or tired, lack of energy, loss of consciousness
ComplicationsAnemia, low blood sugar, dangerously low blood pressure, organ failure
CausesMalnutrition
Diagnostic methodbased on symptoms
Treatmentintensive care

Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death. The term inanition refers to the symptoms and effects of starvation. Starvation may also be used as a means of torture or execution.

According to the World Health Organization (WHO), hunger is the single gravest threat to the world's public health. The WHO also states that malnutrition is by far the biggest contributor to child mortality, present in half of all cases. Undernutrition is a contributory factor in the death of 3.1 million children under five every year. Figures on actual starvation are difficult to come by, but according to the Food and Agriculture Organization, the less severe condition of undernourishment currently affects about 842 million people, or about one in eight (12.5%) people in the world population.

The bloated stomach represents a form of malnutrition called kwashiorkor. The exact pathogenesis of kwashiorkor is not clear, as initially it was thought to relate to diets high in carbohydrates (e.g. maize) but low in protein. While many patients have low albumin, this is thought to be a consequence of the condition. Possible causes such as aflatoxin poisoning, oxidative stress, immune dysregulation, and altered gut microbiota have been suggested. Treatment can help mitigate symptoms such as the pictured weight loss and muscle wasting, however prevention is of utmost importance.

Without any food, humans usually die in around 2 months. There was a surprising case when someone survived 382 days. Lean people can usually survive with a loss of up to 18% of their body mass. Obese people can tolerate more, possibly over 20%. Females survive longer than males.

Signs and symptoms

A girl during the Nigerian Civil War of the late 1960s, shown suffering the effects of severe hunger and malnutrition

The following are some of the symptoms of starvation:

Changes in behaviour or mental status

The beginning stages of starvation impact mental status and behaviours. These symptoms show up as irritable mood, fatigue, trouble concentrating, and preoccupation with food thoughts. People with those symptoms tend to be easily distracted and have no energy.

Physical signs

As starvation progresses, the physical symptoms set in. The timing of these symptoms depends on age, size, and overall health. It usually takes days to weeks, and includes weakness, fast heart rate, shallow breaths that are slowed, thirst, and constipation. There may also be diarrhea in some cases. The eyes begin to sink in and glass over. The muscles begin to become smaller and muscle wasting sets in. One prominent sign in children is a swollen belly. Skin loosens and turns pale in color, and there may be swelling of the feet and ankles.

Weakened immune system

Symptoms of starvation may also appear as a weakened immune system, slow wound healing, and poor response to infection. Rashes may develop on the skin. The body directs any nutrients available to keeping organs functioning.

Other symptoms

Other effects of starvation may include:

Stages of starvation

The symptoms of starvation show up in three stages. Phase one and two can show up in anyone that skips meals, diets, and goes through fasting. Phase three is more severe, can be fatal, and results from long-term starvation.

Phase one: When meals are skipped, the body begins to maintain blood sugar levels by degrading glycogen in the liver and breaking down stored fat and protein. The liver can provide glucose for the first few hours. After that, the body begins to break down fat and protein. The body uses Fatty acids as an energy source for muscles but lowers the amount of glucose sent to the brain. Another chemical that comes from fatty acids is glycerol. It can be used as glucose for energy but eventually runs out.

Phase two: Phase two can last for weeks at a time. In this phase, the body mainly uses stored fat for energy. The breakdown occurs in the liver and turns fat into ketones. After fasting for one week, the brain will use these ketones and any available glucose. Using ketones lowers the need for glucose, and the body slows the breakdown of proteins.

Phase three: By this point, the fat stores are gone, and the body begins to turn to stored protein for energy. This means it needs to break down muscle tissues full of protein; the muscles break down very quickly. Protein is essential for cells to work correctly, and when it runs out, the cells can no longer function.

The cause of death due to starvation is usually an infection or the result of tissue breakdown. This is due to the body becoming unable to produce enough energy to fight off bacteria and viruses. The final stage of starvation includes signals like hair color loss, skin flaking, swelling in the extremities, and a bloated belly. Even though they may feel hunger, people in the final stage of starvation usually cannot eat enough food to recover.

Causes

The body expends more energy than it takes in. This imbalance can arise from one or more medical conditions or circumstantial situations, which can include:

Medical reasons

Circumstantial causes

Biochemistry

With a typical high-carbohydrate diet, the human body relies on free blood glucose as its primary energy source. Glucose can be obtained directly from dietary sugars and by the breakdown of other carbohydrates. In the absence of dietary sugars and carbohydrates, glucose is obtained from the breakdown of stored glycogen. Glycogen is a readily-accessible storage form of glucose, stored in notable quantities in the liver and skeletal muscle.

After the exhaustion of the glycogen reserve, and for the next two to three days, fatty acids become the principal metabolic fuel. At first, the brain continues to use glucose. If a non-brain tissue is using fatty acids as its metabolic fuel, the use of glucose in the same tissue is switched off. Thus, when fatty acids are being broken down for energy, all of the remaining glucose is made available for use by the brain.

After two or three days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for three days, the brain gets 30% of its energy from ketone bodies. After four days, this may increase to 70% or more. Thus, the production of ketone bodies cuts the brain's glucose requirement from 80 g per day to 30 g per day, about 35% of normal, with 65% derived from ketone bodies. But of the brain's remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). This still leaves a deficit of about 10 g of glucose per day that must be supplied from another source; this other source will be the body's own proteins.

After exhaustion of fat stores, the cells in the body begin to break down protein. This releases alanine and lactate produced from pyruvate, which can be converted into glucose by the liver. Since much of human muscle mass is protein, this phenomenon is responsible for the wasting away of muscle mass seen in starvation. However, the body is able to choose which cells will break down protein and which will not. About 2–3 g of protein has to be broken down to synthesize 1 g of glucose; about 20–30 g of protein is broken down each day to make 10 g of glucose to keep the brain alive. However, this number may decrease the longer the fasting period is continued, in order to conserve protein.

Starvation ensues when the fat reserves are completely exhausted and protein is the only fuel source available to the body. Thus, after periods of starvation, the loss of body protein affects the function of important organs, and death results, even if there are still fat reserves left. In a leaner person, the fat reserves are depleted faster, and the protein, sooner, therefore death occurs sooner.) Ultimately, the cause of death is in general cardiac arrhythmia or cardiac arrest, brought on by tissue degradation and electrolyte imbalances. Conditions like metabolic acidosis may also kill starving people.

Prevention

Starvation can be caused by factors beyond the control of the individual. The Rome Declaration on World Food Security outlines several policies aimed at increasing food security and, consequently, preventing starvation. These include:

Supporting farmers in areas of food insecurity through such measures as free or subsidized fertilizers and seeds increases food harvest and reduces food prices.

Treatment

Patients that suffer from starvation can be treated, but this must be done cautiously to avoid refeeding syndrome. Rest and warmth must be provided and maintained. Food can be given gradually in small quantities. The quantity of food can be increased over time. Proteins may be administered intravenously to raise the level of serum proteins. For worse situations, hospice care and opioid medications can be used.

Organizations

Many organizations have been highly effective at reducing starvation in different regions. Aid agencies give direct assistance to individuals, while political organizations pressure political leaders to enact more macro-scale policies that will reduce famine and provide aid.

Statistics

Percentage of population suffering from hunger, World Food Programme, 2020.
  < 2.5%
  < 5.0%
  5.0–14.9%
  15.0–24.9%
  25.0–34.9%
  > 35.0%
  No data

According to estimates by the Food and Agriculture Organization, between 720 and 811 million people were affected by hunger globally in 2020. This was a decrease from estimated 925 million in 2010 and roughly 1 billion in 2009. In 2007, 923 million people were reported as being undernourished, an increase of 80 million since 1990–92. An estimated 820 million people did not have enough to eat in 2018, up from 811 million in the previous year, which is the third year of increase in a row.

As the definitions of starving and malnourished people are different, the number of starving people is different from that of malnourished. Generally, far fewer people are starving than are malnourished.

The proportion of malnourished and starving people in the world has been more or less continually decreasing for at least several centuries. This is due to an increasing supply of food and to overall gains in economic efficiency. In 40 years, the proportion of malnourished people in the developing world has been more than halved. The proportion of starving people has decreased even faster.

Year 1970 1980 1990 2004 2007 2009
Proportion of undernourished people in the less-developed world 37 % 28 % 20 % 16 % 17 % 16 %

Capital punishment


The starving Livilla refusing food.
From a drawing by André Castagne.

Historically, starvation has been used as a death sentence. From the beginning of civilization to the Middle Ages, people were immured, and died for want of food.

In ancient Greco-Roman societies, starvation was sometimes used to dispose of guilty upper-class citizens, especially erring female members of patrician families. In the year 31, Livilla, the niece and daughter-in-law of Tiberius, was discreetly starved to death by her mother for her adulterous relationship with Sejanus and for her complicity in the murder of her own husband, Drusus the Younger.

Another daughter-in-law of Tiberius, named Agrippina the Elder (a granddaughter of Augustus and the mother of Caligula), also died of starvation, in 33 AD; however, it is unclear if her starvation was self-inflicted.

A son and daughter of Agrippina were also executed by starvation for political reasons; Drusus Caesar, her second son, was put in prison in 33 AD, and starved to death by orders of Tiberius (he managed to stay alive for nine days by chewing the stuffing of his bed); Agrippina's youngest daughter, Julia Livilla, was exiled on an island in 41 by her uncle, Emperor Claudius, and her death by starvation was arranged by the empress Messalina.

It is also possible that Vestal Virgins were starved when found guilty of breaking their vows of celibacy.

Ugolino della Gherardesca, his sons, and other members of his family were immured in the Muda, a tower of Pisa, and starved to death in the thirteenth century. Dante, his contemporary, wrote about Gherardesca in his masterpiece The Divine Comedy.

In Sweden in 1317, King Birger of Sweden imprisoned his two brothers for a coup they had staged several years earlier (Nyköping Banquet). According to legend they died of starvation a few weeks later, since their brother had thrown the prison key in the castle moat.

In Cornwall in the UK in 1671, John Trehenban from St Columb Major was condemned to be starved to death in a cage at Castle An Dinas for the murder of two girls.

The Makah, a Native American tribe inhabiting the Pacific Northwest near the modern border of Canada and the United States, practiced death by starvation as a punishment for slaves.

Concentration camps and ghettos

Buchenwald inmates, 16 April 1945, when camp was liberated

Many of the prisoners in the Nazi concentration camps were murdered through deliberate maltreatment, disease, starvation, and overwork, or were executed as unfit for labor. Many occupants of ghettos in eastern Europe also starved to death, most notoriously in the Warsaw Ghetto in German-occupied Poland. Prisoners were transported in inhumane conditions by rail freight cars, in which many died before reaching their destination. The prisoners were confined to the cattle cars for days or even weeks, with little or no food or water. Many died of dehydration in the intense heat of summer or froze to death in winter. Nazi concentration camps in Europe from 1933 to 1945 deliberately underfed prisoners, who were at the same time forced to perform heavy labour. Their diet was restricted to watery vegetable soup and a little bread, with little to no dietary fats, proteins or other essential nutrients. Such treatment led to loss of body tissues, and when prisoners became skeletal, the so-called Muselmanns were murdered by gas or bullets when examined by camp doctors.

Maximilian Kolbe, on a West German postage stamp, marked Auschwitz

Starvation was also used as a punishment where victims were locked into a small cell until dead, a process which could take many days. Saint Maximilian Kolbe, a martyred Polish friar, underwent a sentence of starvation in Auschwitz concentration camp in 1941. Ten prisoners had been condemned to death by starvation in the wake of a successful escape from the camp. Kolbe volunteered to take the place of a man with a wife and children. After two weeks of starvation, Kolbe and three other inmates remained alive; they were then executed with injections of phenol.

Genetic testing

From Wikipedia, the free encyclopedia

Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or through biochemical analysis to measure specific protein output. In a medical setting, genetic testing can be used to diagnose or rule out suspected genetic disorders, predict risks for specific conditions, or gain information that can be used to customize medical treatments based on an individual's genetic makeup. Genetic testing can also be used to determine biological relatives, such as a child's biological parentage (genetic mother and father) through DNA paternity testing, or be used to broadly predict an individual's ancestry. Genetic testing of plants and animals can be used for similar reasons as in humans (e.g. to assess relatedness/ancestry or predict/diagnose genetic disorders), to gain information used for selective breeding, or for efforts to boost genetic diversity in endangered populations.

The variety of genetic tests has expanded throughout the years. Early forms of genetic testing which began in the 1950s involved counting the number of chromosomes per cell. Deviations from the expected number of chromosomes (46 in humans) could lead to a diagnosis of certain genetic conditions such as trisomy 21 (Down syndrome) or monosomy X (Turner syndrome). In the 1970s, a method to stain specific regions of chromosomes, called chromosome banding, was developed that allowed more detailed analysis of chromosome structure and diagnosis of genetic disorders that involved large structural rearrangements. In addition to analyzing whole chromosomes (cytogenetics), genetic testing has expanded to include the fields of molecular genetics and genomics which can identify changes at the level of individual genes, parts of genes, or even single nucleotide "letters" of DNA sequence. According to the National Institutes of Health, there are tests available for more than 2,000 genetic conditions, and one study estimated that as of 2018 there were more than 68,000 genetic tests on the market.

Types

Genetic testing is "the analysis of chromosomes (DNA), proteins, and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes." It can provide information about a person's genes and chromosomes throughout life.

Diagnostic testing

  • Cell-free fetal DNA (cffDNA) testing - a non-invasive (for the fetus) test. It is performed on a sample of venous blood from the mother, and can provide information about the fetus early in pregnancy. As of 2015 it is the most sensitive and specific screening test for Down syndrome.
  • Newborn heel-prick blood sample collection
     
    Newborn screening - used just after birth to identify genetic disorders that can be treated early in life. A blood sample is collected with a heel prick from the newborn 24–48 hours after birth and sent to the lab for analysis. In the United States, newborn screening procedure varies state by state, but all states by law test for at least 21 disorders. If abnormal results are obtained, it does not necessarily mean the child has the disorder. Diagnostic tests must follow the initial screening to confirm the disease. The routine testing of infants for certain disorders is the most widespread use of genetic testing—millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental illness if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). People with PKU do not have an enzyme needed to process the amino acid phenylalanine, which is responsible for normal growth in children and normal protein use throughout their lifetime. If there is a buildup of too much phenylalanine, brain tissue can be damaged, causing developmental delay. Newborn screening can detect the presence of PKU, allowing children to be placed on special diets to avoid the effects of the disorder.
  • Diagnostic testing - used to diagnose or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical mutations and symptoms. Diagnostic testing can be performed at any time during a person's life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person's choices about health care and the management of the disease. For example, people with a family history of polycystic kidney disease (PKD) who experience pain or tenderness in their abdomen, blood in their urine, frequent urination, pain in the sides, a urinary tract infection or kidney stones may decide to have their genes tested and the result could confirm the diagnosis of PKD. Despite the several implications of genetic testing in conditions such as epilepsy or neurodevelopmental disorders, many patients (specially adults) do not have access to these modern diagnostic approaches, showing a relevant diagnostic gap
  • Carrier testing - used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple's risk of having a child with a genetic condition like cystic fibrosis.
  • Preimplantation genetic diagnosis - performed on human embryos prior to the implantation as part of an in vitro fertilization procedure. Pre-implantation testing is used when individuals try to conceive a child through in vitro fertilization. Eggs from the woman and sperm from the man are removed and fertilized outside the body to create multiple embryos. The embryos are individually screened for abnormalities, and the ones without abnormalities are implanted in the uterus.
    • Small amounts of the chorionic villi are sampled during CVS
       
      Prenatal diagnosis - used to detect changes in a fetus's genes or chromosomes before birth. This type of testing is offered to couples with an increased risk of having a baby with a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple's uncertainty or help them decide whether to abort the pregnancy. It cannot identify all possible inherited disorders and birth defects, however. One method of performing a prenatal genetic test involves an amniocentesis, which removes a sample of fluid from the mother's amniotic sac 15 to 20 or more weeks into pregnancy. The fluid is then tested for chromosomal abnormalities such as Down syndrome (Trisomy 21) and Trisomy 18, which can result in neonatal or fetal death. Test results can be retrieved within 7–14 days after the test is done. This method is 99.4% accurate at detecting and diagnosing fetal chromosome abnormalities. There is a slight risk of miscarriage with this test, about 1:400. Another method of prenatal testing is Chorionic Villus Sampling (CVS). Chorionic villi are projections from the placenta that carry the same genetic makeup as the baby. During this method of prenatal testing, a sample of chorionic villi is removed from the placenta to be tested. This test is performed 10–13 weeks into pregnancy and results are ready 7–14 days after the test was done. Another test using blood taken from the fetal umbilical cord is percutaneous umbilical cord blood sampling.
    • Predictive and presymptomatic testing - used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person's chances of developing disorders with a genetic basis, such as certain types of cancer. For example, an individual with a mutation in BRCA1 has a 65% cumulative risk of breast cancer. Hereditary breast cancer along with ovarian cancer syndrome are caused by gene alterations in the genes BRCA1 and BRCA2. Major cancer types related to mutations in these genes are female breast cancer, ovarian, prostate, pancreatic, and male breast cancer. Li-Fraumeni syndrome is caused by a gene alteration on the gene TP53. Cancer types associated with a mutation on this gene include breast cancer, soft tissue sarcoma, osteosarcoma (bone cancer), leukemia and brain tumors. In the Cowden syndrome there is a mutation on the PTEN gene, causing potential breast, thyroid or endometrial cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person's risk of developing a specific disorder, help with making decisions about medical care and provide a better prognosis.
    • Pharmacogenomics - determines the influence of genetic variation on drug response. When a person has a disease or health condition, pharmacogenomics can examine an individual's genetic makeup to determine what medicine and what dosage would be the safest and most beneficial to the patient. In the human population, there are approximately 11 million single nucleotide polymorphisms (SNPs) in people's genomes, making them the most common variations in the human genome. SNPs reveal information about an individual's response to certain drugs. This type of genetic testing can be used for cancer patients undergoing chemotherapy. A sample of the cancer tissue can be sent in for genetic analysis by a specialized lab. After analysis, information retrieved can identify mutations in the tumor which can be used to determine the best treatment option.

    Non-diagnostic testing

    • Forensic testing - uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).
    • Paternity testing - uses special DNA markers to identify the same or similar inheritance patterns between related individuals. Based on the fact that we all inherit half of our DNA from the father, and half from the mother, DNA scientists test individuals to find the match of DNA sequences at some highly differential markers to draw the conclusion of relatedness.
    • Genealogical DNA test - used to determine ancestry or ethnic heritage for genetic genealogy.
    • Research testing - includes finding unknown genes, learning how genes work and advancing understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers.

    Medical procedure

    Genetic testing is often done as part of a genetic consultation and as of mid-2008 there were more than 1,200 clinically applicable genetic tests available. Once a person decides to proceed with genetic testing, a medical geneticist, genetic counselor, primary care doctor, or specialist can order the test after obtaining informed consent.

    Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a medical procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. Alternatively, a small amount of saline mouthwash may be swished in the mouth to collect the cells. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorders, often using DNA sequencing. The laboratory reports the test results in writing to a person's doctor or genetic counselor.

    Routine newborn screening tests are done on a small blood sample obtained by pricking the baby's heel with a lancet.

    Risks and limitations

    The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but non-negligible risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus.

    Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. The potential negative impact of genetic testing has led to an increasing recognition of a "right not to know". In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern. Some individuals avoid genetic testing out of fear it will affect their ability to purchase insurance or find a job. Health insurers do not currently require applicants for coverage to undergo genetic testing, and when insurers encounter genetic information, it is subject to the same confidentiality protections as any other sensitive health information. In the United States, the use of genetic information is governed by the Genetic Information Nondiscrimination Act (GINA) (see discussion below in the section on government regulation).

    Genetic testing can provide only limited information about an inherited condition. The test often can't determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed.

    Another limitation to genetic testing for a hereditary linked cancer, is the variants of unknown clinical significance. Because the human genome has over 22,000 genes, there are 3.5 million variants in the average person's genome. These variants of unknown clinical significance means there is a change in the DNA sequence, however the increase for cancer is unclear because it is unknown if the change affects the gene's function.

    A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision.

    Other risks include incidental findings—a discovery of some possible problem found while looking for something else. In 2013 the American College of Medical Genetics and Genomics (ACMG) that certain genes always be included any time a genomic sequencing was done, and that labs should report the results.

    DNA studies have been criticised for a range of methodological problems and providing misleading, interpretations on racial classifications.

    Direct-to-consumer genetic testing

    Direct-to-consumer (DTC) genetic testing (also called at-home genetic testing) is a type of genetic test that is accessible directly to the consumer without having to go through a health care professional. Usually, to obtain a genetic test, health care professionals such as physicians, nurse practitioners, or genetic counselors acquire their patient's permission and then order the desired test, which may or may not be covered by health insurance. DTC genetic tests, however, allow consumers to bypass this process and purchase DNA tests themselves. DTC genetic testing can entail primarily genealogical/ancestry-related information, health and trait-related information, or both.

    There is a variety of DTC tests, ranging from tests for breast cancer alleles to mutations linked to cystic fibrosis. Possible benefits of DTC testing are the accessibility of tests to consumers, promotion of proactive healthcare, and the privacy of genetic information. Possible additional risks of DTC testing are the lack of governmental regulation, the potential misinterpretation of genetic information, issues related to testing minors, privacy of data, and downstream expenses for the public health care system. In the United States, most DTC genetic test kits are not reviewed by the Food and Drug Administration (FDA), with the exception of a few tests offered by the company 23andMe. As of 2019, the tests that have received marketing authorization by the FDA include 23andMe's genetic health risk reports for select variants of BRCA1/BRCA2, pharmacogenetic reports that test for selected variants associated with metabolism of certain pharmaceutical compounds, a carrier screening test for Bloom syndrome, and genetic health risk reports for a handful of other medical conditions, such as celiac disease and late-onset Alzheimer's.

    Controversy

    DTC genetic testing has been controversial due to outspoken opposition within the medical community. Critics of DTC testing argue against the risks involved, the unregulated advertising and marketing claims, the potential reselling of genetic data to third parties, and the overall lack of governmental oversight.

    DTC testing involves many of the same risks associated with any genetic test. One of the more obvious and dangerous of these is the possibility of misreading of test results. Without professional guidance, consumers can potentially misinterpret genetic information, causing them to be deluded about their personal health.

    Some advertising for DTC genetic testing has been criticized as conveying an exaggerated and inaccurate message about the connection between genetic information and disease risk, utilizing emotions as a selling factor. An advertisement for a BRCA-predictive genetic test for breast cancer stated: “There is no stronger antidote for fear than information.” Apart from rare diseases that are directly caused by specific, single-gene mutation, diseases "have complicated, multiple genetic links that interact strongly with personal environment, lifestyle, and behavior."

    Ancestry.com, a company providing DTC DNA tests for genealogy purposes, has reportedly allowed the warrantless search of their database by police investigating a murder. The warrantless search led to a search warrant to force the gathering of a DNA sample from a New Orleans filmmaker; however he turned out not to be a match for the suspected killer.

    Governmental genetic testing

    In Estonia

    As part of its healthcare system, Estonia is offering all of its residents genome-wide genotyping. This will be translated into personalized reports for use in everyday medical practice via the national e-health portal.

    The aim is to minimise health problems by warning participants most at risk of conditions such as cardiovascular disease and diabetes. It is also hoped that participants who are given early warnings will adopt healthier lifestyles or take preventative drugs.

    Private genetic testing

    Genetic testing has also been taken on by private companies, such as 23andMe, Ancestry.com, and Family Tree DNA. These companies will send the consumer a kit at their home address, with which they will provide a saliva sample for their lab to analyze. The company will then send back the consumer’s results in a few weeks, which is a breakdown of their ancestral heritage and possible health risks that accompany it. Other companies, like National Geographic, have conducted public DNA surveys in an effort to better understand global ancestry and heritage. In 2005, National Geographic launched the Genographic Project, which was a fifteen year project that was discontinued in 2020. Over one million people participated in the DNA sampling from more than 140 countries, which made the project the largest of its kind ever conducted. The project asked for DNA samples from indigenous people as well as the general public, which spurred political controversy among some indigenous groups, leading to the coining of the term "biocolonialism".

    Government regulation

    In the United States

    With regard to genetic testing and information in general, legislation in the United States called the Genetic Information Nondiscrimination Act prohibits group health plans and health insurers from denying coverage to a healthy individual or charging that person higher premiums based solely on a genetic predisposition to developing a disease in the future. The legislation also bars employers from using individuals’ genetic information when making hiring, firing, job placement, or promotion decisions. Although GINA protects against genetic discrimination, Section 210 of the law states that once the disease has manifested, employers can use the medical information and not be in violation of the law, even if the condition has a genetic basis. The legislation, the first of its kind in the United States, was passed by the United States Senate on April 24, 2008, on a vote of 95–0, and was signed into law by President George W. Bush on May 21, 2008. It went into effect on November 21, 2009.

    In June 2013 the US Supreme Court issued two rulings on human genetics. The Court struck down patents on human genes, opening up competition in the field of genetic testing. The Supreme Court also ruled that police were allowed to collect DNA from people arrested for serious offenses.

    In the European Union

    Effective as of 25 May 2018, companies that process genetic data must abide by the General Data Protection Regulation (GDPR). The GDPR is a set of rules/regulations that helps an individual take control of their data information that is collected, used and stored digitally or in a structured filing system on paper, and restricts a company's use of personal data. The regulation also applies to companies who offer products/services outside of the EU.

    In Russia

    Articles 10 and 11 of the Federal Law of July 27, 2006 No. 152-FZ "On Personal Data" provide that the processing of special categories of personal data relating to race, nationality, political views, religious or philosophical beliefs, health status, intimate life is allowed if it is necessary in connection with the implementation of international agreements of the Russian Federation on readmission and is carried out in accordance with the legislation of the Russian Federation on citizenship of the Russian Federation. Information characterizing the physiological and biological characteristics of a person, on the basis of which it is possible to establish his identity (biometric personal data), can be processed without the consent of the subject of personal data in connection with the implementation of international agreements of the Russian Federation on readmission, administration of justice and execution of judicial acts, compulsory state fingerprinting registration, as well as in cases stipulated by the legislation of the Russian Federation on defense, security, anti-terrorism, transport security, anti-corruption, operational investigative activities, public service, as well as in cases stipulated by the criminal-executive legislation of Russia, the legislation of Russia on the procedure for leaving the Russian Federation and entering the Russian Federation, citizenship of the Russian Federation and notaries.

    In Russia, scientific DNA testing is being actively carried out in order to study the genetic diversity of the peoples of Russia in the framework of the state task - to learn from DNA to determine the probable territory of human origin based on data on the majority of the peoples of the country. On June 16, 2017, the Council of Ministers of the Union State of Belarus and Russia adopted Resolution No. 26, in which it approved the scientific and technical program of the Union State "Development of innovative genogeographic and genomic technologies for identification of personality and individual characteristics of a person based on the study of gene pools of the regions of the Union State" (DNA- identification).

    Within the framework of this program, it is also planned to include the peoples of neighboring countries, which are the main source of migration, into the genogeographic study on the basis of existing collections.

    In popular culture

    Some possible future ethical problems of genetic testing were considered in the science fiction film Gattaca, the novel Next, and the science fiction anime series Mobile Suit Gundam Seed. Also, some films which include the topic of genetic testing include The Island, Halloween: The Curse of Michael Myers, and the Resident Evil series.

    Children & Religion

    Three to five percent of the funding available for the Human Genome Project was set aside to study the many social, ethical, and legal implications that will result from the better understanding of human heredity the rapid expansion of genetic risk assessment by genetic testing which would be facilitated by this project.

    Pediatric genetic testing

    The American Academy of Pediatrics (AAP) and the American College of Medical Genetics (ACMG) have provided new guidelines for the ethical issue of pediatric genetic testing and screening of children in the United States. Their guidelines state that performing pediatric genetic testing should be in the best interest of the child. AAP and ACMG recommend holding off on genetic testing for late-onset conditions until adulthood, unless diagnosing genetic disorders during childhood can reduce morbidity or mortality (e.g., to start early intervention). Testing asymptomatic children who are at risk of childhood onset conditions can also be warranted. Both AAP and ACMG discourage the use of direct-to-consumer and home kit genetic tests because of concerns regarding the accuracy, interpretation and oversight of test content. Guidelines also state that parents or guardians should be encouraged to inform their child of the results from the genetic test if the minor is of appropriate age. For ethical and legal reasons, health care providers should be cautious in providing minors with predictive genetic testing without the involvement of parents or guardians. Within the guidelines set by AAP and ACMG, health care providers have an obligation to inform parents or guardians on the implication of test results. AAP and ACMG state that any type of predictive genetic testing should be offered with genetic counseling by clinical genetics, genetic counselors or health care providers.

    Israel

    In Israel, uses of DNA testing to determine if people are eligible for immigration. The policy where "many Jews from the Former Soviet Union (‘FSU’) are asked to provide DNA confirmation of their Jewish heritage in the form of paternity tests in order to immigrate as Jews and become citizens under Israel's Law of Return" has generated controversy.

    Costs & Time

    The cost of genetic testing can range from under $100 to more than $2,000. This depends on the complexity of the test. The cost will increase if more than one test is necessary or if multiple family members are getting tested to obtain additional results. Costs can vary by state and some states cover part of the total cost.

    From the date that a sample is taken, results may take weeks to months, depending upon the complexity and extent of the tests being performed. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. Prior to the testing, the doctor or genetic counselor who is requesting a particular test can provide specific information about the cost and time frame associated with that test.

    Notable people

    • Michiei Oto, Japanese molecular biologist and genetic testing expert

    Sunday, June 4, 2023

    Human genetic enhancement

    From Wikipedia, the free encyclopedia
     
    An illustration of viral vector-mediated gene transfer using an adenovirus as the vector.

    Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases (gene therapy), prevent the possibility of getting a particular disease (similarly to vaccines), to improve athlete performance in sporting events (gene doping), or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable (which has raised concerns within the scientific community).

    Gene therapy

    Genetic modification in order to cure genetic diseases is referred to as gene therapy. Many such gene therapies are available, made it through all phases of clinical research and are approved by the FDA. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I. As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

    Disease prevention

    Some people are immunocompromised and their bodies are hence much less capable of fending off and defeating diseases (i.e. influenza, ...). In some cases this is due to genetic flaws or even genetic diseases such as SCID. Some gene therapies have already been developed or are being developed to correct these genetic flaws/diseases, hereby making these people less susceptible to catching additional diseases (i.e. influenza, ...).

    In November 2018, Lulu and Nana were created. By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called CCR5 in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus.

    Gene doping

    Athletes might adopt gene therapy technologies to improve their performance. Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.

    Other uses

    Other hypothetical gene therapies could include changes to physical appearance, metabolism, mental faculties such as memory and intelligence, and well-being (by increasing resistance to depression or relieving chronic pain, for example).

    Physical appearance

    Some congenital disorders (such as those affecting the muscoskeletal system) may affect physical appearance, and in some cases may also cause physical discomfort. Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these diseases) may prevent this.

    Also changes in the mystatin gene may alter appearance.

    Behavior

    Behavior may also be modified by genetic intervention. Some people may be aggressive, selfish, and may not be able to function well in society. There is currently research ongoing on genes that are or may be (in part) responsible for selfishness (e.g. ruthlessness gene), aggression (e.g. warrior gene), altruism (e.g. OXTR, CD38, COMT, DRD4, DRD5, IGF2, GABRB2)

    There is some research going on on the hypothetical treatment of psychiatric disorders by means of gene therapy. It is assumed that, with gene-transfer techniques, it is possible (in experimental settings using animal models) to alter CNS gene expression and thereby the intrinsic generation of molecules involved in neural plasticity and neural regeneration, and thereby modifying ultimately behaviour.

    In recent years, it was possible to modify ethanol intake in animal models. Specifically, this was done by targeting the expression of the aldehyde dehydrogenase gene (ALDH2), lead to a significantly altered alcohol-drinking behaviour. Reduction of p11, a serotonin receptor binding protein, in the nucleus accumbens led to depression-like behaviour in rodents, while restoration of the p11 gene expression in this anatomical area reversed this behaviour.

    Recently, it was also shown that the gene transfer of CBP (CREB (c-AMP response element binding protein) binding protein) improves cognitive deficits in an animal model of Alzheimer's dementia via increasing the expression of BDNF (brain-derived neurotrophic factor). The same authors were also able to show in this study that accumulation of amyloid-β (Aβ) interfered with CREB activity which is physiologically involved in memory formation.

    In another study, it was shown that Aβ deposition and plaque formation can be reduced by sustained expression of the neprilysin (an endopeptidase) gene which also led to improvements on the behavioural (i.e. cognitive) level.

    Similarly, the intracerebral gene transfer of ECE (endothelin-converting enzyme) via a virus vector stereotactically injected in the right anterior cortex and hippocampus, has also shown to reduce Aβ deposits in a transgenic mouse model of Alzeimer's dementia.

    There is also research going on on genoeconomics, a protoscience that is based on the idea that a person's financial behavior could be traced to their DNA and that genes are related to economic behavior. As of 2015, the results have been inconclusive. Some minor correlations have been identified.

    Databases about potential modifications

    George Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against Alzheimer's disease, disease resistances, higher lean muscle mass and enhanced learning abilities along with some of the associated studies and potential negative effects.

    An illustration of viral vector-mediated gene transfer using an adenovirus as the vector.

    Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases (gene therapy), prevent the possibility of getting a particular disease (similarly to vaccines), to improve athlete performance in sporting events (gene doping), or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable (which has raised concerns within the scientific community).

    Gene therapy

    Genetic modification in order to cure genetic diseases is referred to as gene therapy. Many such gene therapies are available, made it through all phases of clinical research and are approved by the FDA. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I. As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

    Disease prevention

    Some people are immunocompromised and their bodies are hence much less capable of fending off and defeating diseases (i.e. influenza, ...). In some cases this is due to genetic flaws or even genetic diseases such as SCID. Some gene therapies have already been developed or are being developed to correct these genetic flaws/diseases, hereby making these people less susceptible to catching additional diseases (i.e. influenza, ...).

    In November 2018, Lulu and Nana were created. By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called CCR5 in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus.

    Gene doping

    Athletes might adopt gene therapy technologies to improve their performance. Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.

    Other uses

    Other hypothetical gene therapies could include changes to physical appearance, metabolism, mental faculties such as memory and intelligence, and well-being (by increasing resistance to depression or relieving chronic pain, for example).

    Physical appearance

    Some congenital disorders (such as those affecting the muscoskeletal system) may affect physical appearance, and in some cases may also cause physical discomfort. Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these diseases) may prevent this.

    Also changes in the mystatin gene may alter appearance.

    Behavior

    Behavior may also be modified by genetic intervention. Some people may be aggressive, selfish, and may not be able to function well in society. There is currently research ongoing on genes that are or may be (in part) responsible for selfishness (e.g. ruthlessness gene), aggression (e.g. warrior gene), altruism (e.g. OXTR, CD38, COMT, DRD4, DRD5, IGF2, GABRB2)

    There is some research going on on the hypothetical treatment of psychiatric disorders by means of gene therapy. It is assumed that, with gene-transfer techniques, it is possible (in experimental settings using animal models) to alter CNS gene expression and thereby the intrinsic generation of molecules involved in neural plasticity and neural regeneration, and thereby modifying ultimately behaviour.

    In recent years, it was possible to modify ethanol intake in animal models. Specifically, this was done by targeting the expression of the aldehyde dehydrogenase gene (ALDH2), lead to a significantly altered alcohol-drinking behaviour. Reduction of p11, a serotonin receptor binding protein, in the nucleus accumbens led to depression-like behaviour in rodents, while restoration of the p11 gene expression in this anatomical area reversed this behaviour.

    Recently, it was also shown that the gene transfer of CBP (CREB (c-AMP response element binding protein) binding protein) improves cognitive deficits in an animal model of Alzheimer's dementia via increasing the expression of BDNF (brain-derived neurotrophic factor). The same authors were also able to show in this study that accumulation of amyloid-β (Aβ) interfered with CREB activity which is physiologically involved in memory formation.

    In another study, it was shown that Aβ deposition and plaque formation can be reduced by sustained expression of the neprilysin (an endopeptidase) gene which also led to improvements on the behavioural (i.e. cognitive) level.

    Similarly, the intracerebral gene transfer of ECE (endothelin-converting enzyme) via a virus vector stereotactically injected in the right anterior cortex and hippocampus, has also shown to reduce Aβ deposits in a transgenic mouse model of Alzeimer's dementia.

    There is also research going on on genoeconomics, a protoscience that is based on the idea that a person's financial behavior could be traced to their DNA and that genes are related to economic behavior. As of 2015, the results have been inconclusive. Some minor correlations have been identified.

    Databases about potential modifications

    George Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against Alzheimer's disease, disease resistances, higher lean muscle mass and enhanced learning abilities along with some of the associated studies and potential negative effects.

    Quantification of margins and uncertainties

    From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Quantification_of_margins_and_uncertainties...