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Animal Biotechnology | Bioscience Topics | About Bioscience

Posted: October 21, 2016 at 6:41 am

Related Links http://www.bbsrc.ac.uk

The Biotechnology and Biological Sciences Research Council (BBSRC) is the United Kingdoms principal funder of basic and strategic biological research. To deliver its mission, the BBSRC supports research and training in universities and research centers and promotes knowledge transfer from research to applications in business, industry and policy, and public engagement in the biosciences. The site contains extensive articles on the ethical and social issues involved in animal biotechnology.

The Department of Agriculture (USDA) provides leadership on food, agriculture, natural resources and related issues through public policy, the best available science and efficient management. The National Institute of Food and Agriculture is part of the USDA; its site contains information about the science behind animal biotechnology and a glossary of terms. Related topics also are searchable, including animal breeding, genetics and many others.

The Pew Initiative on Food and Biotechnology is an independent, objective source of information on agricultural biotechnology. Funded by a grant from the Pew Charitable Trusts to the University of Richmond, it advocates neither for nor against agricultural biotechnology. Instead, the initiative is committed to providing information and encouraging dialogue so consumers and policy-makers can make their own informed decisions.

Animal biotechnology is the use of science and engineering to modify living organisms. The goal is to make products, to improve animals and to develop microorganisms for specific agricultural uses.

Examples of animal biotechnology include creating transgenic animals (animals with one or more genes introduced by human intervention), using gene knock out technology to make animals with a specific inactivated gene and producing nearly identical animals by somatic cell nuclear transfer (or cloning).

The animal biotechnology in use today is built on a long history. Some of the first biotechnology in use includes traditional breeding techniques that date back to 5000 B.C.E. Such techniques include crossing diverse strains of animals (known as hybridizing) to produce greater genetic variety. The offspring from these crosses then are bred selectively to produce the greatest number of desirable traits. For example, female horses have been bred with male donkeys to produce mules, and male horses have been bred with female donkeys to produce hinnies, for use as work animals, for the past 3,000 years. This method continues to be used today.

The modern era of biotechnology began in 1953, when American biochemist James Watson and British biophysicist Francis Crick presented their double-helix model of DNA. That was followed by Swiss microbiologist Werner Arbers discovery in the 1960s of special enzymes, called restriction enzymes, in bacteria. These enzymes cut the DNA strands of any organism at precise points. In 1973, American geneticist Stanley Cohen and American biochemist Herbert Boyer removed a specific gene from one bacterium and inserted it into another using restriction enzymes. That event marked the beginning of recombinant DNA technology, or genetic engineering. In 1977, genes from other organisms were transferred to bacteria, an achievement that led eventually to the first transfer of a human gene.

Animal biotechnology in use today is based on the science of genetic engineering. Under the umbrella of genetic engineering exist other technologies, such as transgenics and cloning, that also are used in animal biotechnology.

Transgenics (also known as recombinant DNA) is the transferal of a specific gene from one organism to another. Gene splicing is used to introduce one or more genes of an organism into a second organism. A transgenic animal is created once the second organism incorporates the new DNA into its own genetic material.

In gene splicing, DNA cannot be transferred directly from its original organism, the donor, to the recipient organism, or the host. Instead, the donor DNA must be cut and pasted, or recombined, into a compatible fragment of DNA from a vector an organism that can carry the donor DNA into the host. The host organism often is a rapidly multiplying microorganism such as a harmless bacterium, which serves as a factory where the recombined DNA can be duplicated in large quantities. The subsequently produced protein then can be removed from the host and used as a genetically engineered product in humans, other animals, plants, bacteria or viruses. The donor DNA can be introduced directly into an organism by techniques such as injection through the cell walls of plants or into the fertilized egg of an animal.

This transferring of genes alters the characteristics of the organism by changing its protein makeup. Proteins, including enzymes and hormones, perform many vital functions in organisms. Individual genes direct an animals characteristics through the production of proteins.

Scientists use reproductive cloning techniques to produce multiple copies of mammals that are nearly identical copies of other animals, including transgenic animals, genetically superior animals and animals that produce high quantities of milk or have some other desirable trait. To date, cattle, sheep, pigs, goats, horses, mules, cats, rats and mice have been cloned, beginning with the first cloned animal, a sheep named Dolly, in 1996.

Reproductive cloning begins with somatic cell nuclear transfer (SCNT). In SCNT, scientists remove the nucleus from an egg cell (oocyte) and replace it with a nucleus from a donor adult somatic cell, which is any cell in the body except for an oocyte or sperm. For reproductive cloning, the embryo is implanted into a uterus of a surrogate female, where it can develop into a live being.

In addition to the use of transgenics and cloning, scientists can use gene knock out technology to inactivate, or knock out, a specific gene. It is this technology that creates a possible source of replacement organs for humans. The process of transplanting cells, tissues or organs from one species to another is referred to as xenotransplantation. Currently, the pig is the major animal being considered as a viable organ donor to humans. Unfortunately, pig cells and human cells are not immunologically compatible. Pigs, like almost all mammals, have markers on their cells that enable the human immune system to recognize them as foreign and reject them. Genetic engineering is used to knock out the pig gene responsible for the protein that forms the marker to the pig cells.

Animal biotechnology has many potential uses. Since the early 1980s, transgenic animals have been created with increased growth rates, enhanced lean muscle mass, enhanced resistance to disease or improved use of dietary phosphorous to lessen the environmental impacts of animal manure. Transgenic poultry, swine, goats and cattle that generate large quantities of human proteins in eggs, milk, blood or urine also have been produced, with the goal of using these products as human pharmaceuticals. Human pharmaceutical proteins include enzymes, clotting factors, albumin and antibodies. The major factor limiting the widespread use of transgenic animals in agricultural production systems is their relatively inefficient production rate (a success rate of less than 10 percent).

A specific example of these particular applications of animal biotechnology is the transfer of the growth hormone gene of rainbow trout directly into carp eggs. The resulting transgenic carp produce both carp and rainbow trout growth hormones and grow to be one-third larger than normal carp. Another example is the use of transgenic animals to clone large quantities of the gene responsible for a cattle growth hormone. The hormone is extracted from the bacterium, is purified and is injected into dairy cows, increasing their milk production by 10 to 15 percent. That growth hormone is called bovine somatotropin or BST.

Another major application of animal biotechnology is the use of animal organs in humans. Pigs currently are used to supply heart valves for insertion into humans, but they also are being considered as a potential solution to the severe shortage in human organs available for transplant procedures.

While predicting the future is inherently risky, some things can be said with certainty about the future of animal biotechnology. The government agencies involved in the regulation of animal biotechnology, mainly the Food and Drug Administration (FDA), likely will rule on pending policies and establish processes for the commercial uses of products created through the technology. In fact, as of March 2006, the FDA was expected to rule in the next few months on whether to approve meat and dairy products from cloned animals for sale to the public. If these animals and animal products are approved for human consumption, several companies reportedly are ready to sell milk, and perhaps meat, from cloned animals most likely cattle and swine. It also is expected that technologies will continue to be developed in the field, with much hope for advances in the use of animal organs in human transplant operations.

The potential benefits of animal biotechnology are numerous and include enhanced nutritional content of food for human consumption; a more abundant, cheaper and varied food supply; agricultural land-use savings; a decrease in the number of animals needed for the food supply; improved health of animals and humans; development of new, low-cost disease treatments for humans; and increased understanding of human disease.

Yet despite these potential benefits, several areas of concern exist around the use of biotechnology in animals. To date, a majority of the American public is uncomfortable with genetic modifications to animals.

According to a survey conducted by the Pew Initiative on Food and Biotechnology, 58 percent of those polled said they opposed scientific research on the genetic engineering of animals. And in a Gallup poll conducted in May 2004, 64 percent of Americans polled said they thought it was morally wrong to clone animals.

Concerns surrounding the use of animal biotechnology include the unknown potential health effects to humans from food products created by transgenic or cloned animals, the potential effects on the environment and the effects on animal welfare.

Before animal biotechnology will be used widely by animal agriculture production systems, additional research will be needed to determine if the benefits of animal biotechnology outweigh these potential risks.

The main question posed about the safety of food produced through animal biotechnology for human consumption is, Is it safe to eat? But answering that question isnt simple. Other questions must be answered first, such as, What substances expressed as a result of the genetic modification are likely to remain in food? Despite these questions, the National Academies of Science (NAS) released a report titled Animal Biotechnology: Science-Based Concerns stating that the overall concern level for food safety was determined to be low. Specifically, the report listed three specific food concerns: allergens, bioactivity and the toxicity of unintended expression products.

The potential for new allergens to be expressed in the process of creating foods from genetically modified animals is a real and valid concern, because the process introduces new proteins. While food allergens are not a new issue, the difficulty comes in how to anticipate these adequately, because they only can be detected once a person is exposed and experiences a reaction.

Another food safety issue, bioactivity, asks, Will putting a functional protein like a growth hormone in an animal affect the person who consumes food from that animal? As of May 2006, scientists cannot say for sure if the proteins will.

Finally, concern exists about the toxicity of unintended expression products in the animal biotechnology process. While the risk is considered low, there is no data available. The NAS report stated it still needs be proven that the nutritional profile does not change in these foods and that no unintended and potentially harmful expression products appear.

Another major concern surrounding the use of animal biotechnology is the potential for negative impact to the environment. These potential harms include the alteration of the ecologic balance regarding feed sources and predators, the introduction of transgenic animals that alter the health of existing animal populations and the disruption of reproduction patterns and their success.

To assess the risk of these environmental harms, many more questions must be answered, such as: What is the possibility the altered animal will enter the environment? Will the animals introduction change the ecological system? Will the animal become established in the environment? and Will it interact with and affect the success of other animals in the new community? Because of the many uncertainties involved, it is challenging to make an assessment.

To illustrate a potential environmental harm, consider that if transgenic salmon with genes engineered to accelerate growth were released into the natural environment, they could compete more successfully for food and mates than wild salmon. Thus, there also is concern that genetically engineered organisms will escape and reproduce in the natural environment. It is feared existing species could be eliminated, thus upsetting the natural balance of organisms.

The regulation of animal biotechnology currently is performed under existing government agencies. To date, no new regulations or laws have been enacted to deal with animal biotechnology and related issues. The main governing body for animal biotechnology and their products is the FDA. Specifically, these products fall under the new animal drug provisions of the Food, Drug, and Cosmetic Act (FDCA). In this use, the introduced genetic construct is considered the drug. This lack of concrete regulatory guidance has produced many questions, especially because the process for bringing genetically engineered animals to market remains unknown.

Currently, the only genetically engineered animal on the market is the GloFish, a transgenic aquarium fish engineered to glow in the dark. It has not been subject to regulation by the FDA, however, because it is not believed to be a threat to the environment.

Many people question the use of an agency that was designed specifically for drugs to regulate live animals. The agencys strict confidentiality provisions and lack of an environmental mandate in the FDCA also are concerns. It still is unclear how the agencys provisions will be interpreted for animals and how multiple agencies will work together in the regulatory system.

When animals are genetically engineered for biomedical research purposes (as pigs are, for example, in organ transplantation studies), their care and use is carefully regulated by the Department of Agriculture. In addition, if federal funds are used to support the research, the work further is regulated by the Public Health Service Policy on Humane Care and Use of Laboratory Animals.

Whether products generated from genetically engineered animals should be labeled is yet another controversy surrounding animal biotechnology. Those opposed to mandatory labeling say it violates the governments traditional focus on regulating products, not processes. If a product of animal biotechnology has been proven scientifically by the FDA to be safe for human consumption and the environment and not materially different from similar products produced via conventional means, these individuals say it is unfair and without scientific rationale to single out that product for labeling solely because of the process by which it was made.

On the other hand, those in favor of mandatory labeling argue labeling is a consumer right-to-know issue. They say consumers need full information about products in the marketplace including the processes used to make those products not for food safety or scientific reasons, but so they can make choices in line with their personal ethics.

On average, it takes seven to nine years and an investment of about $55 million to develop, test and market a new genetically engineered product. Consequently, nearly all researchers involved in animal biotechnology are protecting their investments and intellectual property through the patent system. In 1988, the first patent was issued on a transgenic animal, a strain of laboratory mice whose cells were engineered to contain a cancer-predisposing gene. Some people, however, are opposed ethically to the patenting of life forms, because it makes organisms the property of companies. Other people are concerned about its impact on small farmers. Those opposed to using the patent system for animal biotechnology have suggested using breed registries to protect intellectual property.

Ethical and social considerations surrounding animal biotechnology are of significant importance. This especially is true because researchers and developers worry the future market success of any products derived from cloned or genetically engineered animals will depend partly on the publics acceptance of those products.

Animal biotechnology clearly has its skeptics as well as its outright opponents. Strict opponents think there is something fundamentally immoral about the processes of transgenics and cloning. They liken it to playing God. Moreover, they often oppose animal biotechnology on the grounds that it is unnatural. Its processes, they say, go against nature and, in some cases, cross natural species boundaries.

Still others question the need to genetically engineer animals. Some wonder if it is done so companies can increase profits and agricultural production. They believe a compelling need should exist for the genetic modification of animals and that we should not use animals only for our own wants and needs. And yet others believe it is unethical to stifle technology with the potential to save human lives.

While the field of ethics presents more questions than it answers, it is clear animal biotechnology creates much discussion and debate among scientists, researchers and the American public. Two main areas of debate focus on the welfare of animals involved and the religious issues related to animal biotechnology.

Perhaps the most controversy and debate regarding animal biotechnology surrounds the animals themselves. While it has been noted that animals might, in fact, benefit from the use of animal biotechnology through improved health, for example the majority of discussion is about the known and unknown potential negative impacts to animal welfare through the process.

For example, calves and lambs produced through in vitro fertilization or cloning tend to have higher birth weights and longer gestation periods, which leads to difficult births that often require cesarean sections. In addition, some of the biotechnology techniques in use today are extremely inefficient at producing fetuses that survive. Of the transgenic animals that do survive, many do not express the inserted gene properly, often resulting in anatomical, physiological or behavioral abnormalities. There also is a concern that proteins designed to produce a pharmaceutical product in the animals milk might find their way to other parts of the animals body, possibly causing adverse effects.

Animal telos is a concept derived from Aristotle and refers to an animals fundamental nature. Disagreement exists as to whether it is ethical to change an animals telos through transgenesis. For example, is it ethical to create genetically modified chickens that can tolerate living in small cages? Those opposed to the concept say it is a clear sign we have gone too far in changing that animal.

Those unopposed to changing an animals telos, however, argue it could benefit animals by fitting them for living conditions for which they are not naturally suited. In this way, scientists could create animals that feel no pain.

Religion plays a crucial part in the way some people view animal biotechnology. For some people, these technologies are considered blasphemous. In effect, God has created a perfect, natural order, they say, and it is sinful to try to improve that order by manipulating the basic ingredient of all life, DNA. Some religions place great importance on the integrity of species, and as a result, those religions followers strongly oppose any effort to change animals through genetic modification.

Not all religious believers make these assertions, however, and different believers of the same religion might hold differing views on the subject. For example, Christians do not oppose animal biotechnology unanimously. In fact, some Christians support animal biotechnology, saying the Bible teaches humanitys dominion over nature. Some modern theologians even see biotechnology as a challenging, positive opportunity for us to work with God as co-creators.

Transgenic animals can pose problems for some religious groups. For example, Muslims, Sikhs and Hindus are forbidden to eat certain foods. Such religious requirements raise basic questions about the identity of animals and their genetic makeup. If, for example, a small amount of genetic material from a fish is introduced into a melon (in order to allow it grow to in lower temperatures), does that melon become fishy in any meaningful sense? Some would argue all organisms share common genetic material, so the melon would not contain any of the fishs identity. Others, however, believe the transferred genes are exactly what make the animal distinctive; therefore the melon would be forbidden to be eaten as well.

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Cancer – Wikipedia

Posted: October 21, 2016 at 6:40 am

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.[1][2] Not all tumors are cancerous; benign tumors do not spread to other parts of the body.[2] Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements.[3] While these symptoms may indicate cancer, they may have other causes.[3] Over 100 cancers affect humans.[2]

Tobacco use is the cause of about 22% of cancer deaths.[1] Another 10% is due to obesity, poor diet, lack of physical activity and drinking alcohol.[1][4] Other factors include certain infections, exposure to ionizing radiation and environmental pollutants.[5] In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C and human papillomavirus (HPV).[1] These factors act, at least partly, by changing the genes of a cell.[6] Typically many genetic changes are required before cancer develops.[6] Approximately 510% of cancers are due to inherited genetic defects from a person's parents.[7] Cancer can be detected by certain signs and symptoms or screening tests.[1] It is then typically further investigated by medical imaging and confirmed by biopsy.[8]

Many cancers can be prevented by not smoking, maintaining a healthy weight, not drinking too much alcohol, eating plenty of vegetables, fruits and whole grains, vaccination against certain infectious diseases, not eating too much processed and red meat, and avoiding too much sunlight exposure.[9][10] Early detection through screening is useful for cervical and colorectal cancer.[11] The benefits of screening in breast cancer are controversial.[11][12] Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy, and targeted therapy.[1][13] Pain and symptom management are an important part of care. Palliative care is particularly important in people with advanced disease.[1] The chance of survival depends on the type of cancer and extent of disease at the start of treatment.[6] In children under 15 at diagnosis the five-year survival rate in the developed world is on average 80%.[14] For cancer in the United States the average five-year survival rate is 66%.[15]

In 2012 about 14.1 million new cases of cancer occurred globally (not including skin cancer other than melanoma).[6] It caused about 8.2 million deaths or 14.6% of human deaths.[6][16] The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer.[6] If skin cancer other than melanoma were included in total new cancers each year it would account for around 40% of cases.[17][18] In children, acute lymphoblastic leukaemia and brain tumors are most common except in Africa where non-Hodgkin lymphoma occurs more often.[14] In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age and many cancers occur more commonly in developed countries.[6] Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world.[19] The financial costs of cancer were estimated at $1.16 trillion US dollars per year as of 2010.[20]

Cancers are a large family of diseases that involve abnormal cell growth with the potential to invade or spread to other parts of the body.[1][2] They form a subset of neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth and will often form a mass or lump, but may be distributed diffusely.[21][22]

All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include:[23]

The progression from normal cells to cells that can form a detectable mass to outright cancer involves multiple steps known as malignant progression.[24][25]

When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer's type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer is a "great imitator". Thus, it is common for people diagnosed with cancer to have been treated for other diseases, which were hypothesized to be causing their symptoms.[26]

Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.[26]

General symptoms occur due to effects that are not related to direct or metastatic spread. These may include: unintentional weight loss, fever, excessive fatigue and changes to the skin.[27]Hodgkin disease, leukemias and cancers of the liver or kidney can cause a persistent fever.[26]

Some cancers may cause specific groups of systemic symptoms, termed paraneoplastic phenomena. Examples include the appearance of myasthenia gravis in thymoma and clubbing in lung cancer.[26]

Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by haematogenous spread via the blood to distant sites, known as metastasis. When cancer spreads by a haematogenous route, it usually spreads all over the body. However, cancer 'seeds' grow in certain selected site only ('soil') as hypothesized in the soil and seed hypothesis of cancer metastasis. The symptoms of metastatic cancers depend on the tumor location and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.[26]

The majority of cancers, some 9095% of cases, are due to environmental factors. The remaining 510% are due to inherited genetics.[5]Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors and not merely pollution.[28] Common environmental factors that contribute to cancer death include tobacco (2530%), diet and obesity (3035%), infections (1520%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity and environmental pollutants.[5]

It is not generally possible to prove what caused a particular cancer, because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease.[29]

Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.

Tobacco smoke, for example, causes 90% of lung cancer.[30] It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas.[31] Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.[32]

Tobacco is responsible about one in five cancer deaths worldwide[32] and about one in three in the developed world[33]Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.[34][35]

In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers.[36] Cancer from work-related substance exposures may cause between 220% of cases,[37] causing at least 200,000 deaths.[38] Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.[38]

Diet, physical inactivity and obesity are related to up to 3035% of cancer deaths.[5][39] In the United States excess body weight is associated with the development of many types of cancer and is a factor in 1420% of cancer deaths.[39] A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country.[40] Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system.[39] More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.

Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer.[41]Aflatoxin B1, a frequent food contaminant, causes liver cancer.[41]Betel nut chewing can cause oral cancer.[41] National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet[42] while colon cancer is more common in the United States. Immigrant cancer profiles develop mirror that of their new country, often within one generation.[43]

Worldwide approximately 18% of cancer deaths are related to infectious diseases.[5] This proportion ranges from a high of 25% in Africa to less than 10% in the developed world.[5]Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.

Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), EpsteinBarr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma.[44][45] Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).[46]

Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation.[5] Additionally, the majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

Ionizing radiation is not a particularly strong mutagen.[47] Residential exposure to radon gas, for example, has similar cancer risks as passive smoking.[47] Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke.[47] Radiation can cause cancer in most parts of the body, in all animals and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.[47]

Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer.[47] It is also used in some kinds of medical imaging.[48]

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies.[49] Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.[49]

Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer.[50] However, studies have not found a consistent link between mobile phone radiation and cancer risk.[51]

The vast majority of cancers are non-hereditary ("sporadic"). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 310% of cancer.[52] Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer,[52] and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer,[53] among others.

Some substances cause cancer primarily through their physical, rather than chemical, effects.[54] A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs.[54] Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects.[54] Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite).[54] Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.[54]

Physical trauma resulting in cancer is relatively rare.[55] Claims that breaking bones resulted in bone cancer, for example, have not been proven.[55] Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer.[55] One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present.[55] Frequent consumption of scalding hot tea may produce esophageal cancer.[55] Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma.[55] However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.

Chronic inflammation has been hypothesized to directly cause mutation.[55][56] Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment.[57][58]Oncogenes build up an inflammatory pro-tumorigenic microenvironment.[59]

Some hormones play a role in the development of cancer by promoting cell proliferation.[60]Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.[61]

Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer.[60] For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene.[60] Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer.[60] Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.[60]

Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.[60] Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones.[60] On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer.[60]Osteosarcoma may be promoted by growth hormones.[60] Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.[60]

There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies.[62] Rates of gastrointestinal cancers are increased in people with Crohn's disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.[63]

Cancer is fundamentally a disease of tissue growth regulation. In order for a normal cell to transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered.[64]

The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.[65]

Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common are mutations, which are changes in the nucleotide sequence of genomic DNA.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Small-scale mutations include point mutations, deletions and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.

Replication of the data contained within the DNA of living cells will probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process and safeguards the cell against cancer. If significant error occurs, the damaged cell can self-destruct through programmed cell death, termed apoptosis. If the error control processes fail, then the mutations will survive and be passed along to daughter cells.

Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation or hypoxia.[66]

The errors that cause cancer are self-amplifying and compounding, for example:

The transformation of a normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the body's design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution, drives progression towards more invasive stages.[67] Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies.

Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.[24][25]

The classical view of cancer is a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes and chromosomal abnormalities. Later epigenetic alterations' role was identified.[68]

Epigenetic alterations refer to functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification[69] and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1).[70] Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, last for multiple generations and can be considered to be epimutations (equivalent to mutations).

Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.[71]

While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers.[72][73][74][75]

Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and cause increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in DNA mismatch repair[76][77] or in homologous recombinational repair (HRR).[78] Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.[79]

Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.[80][81]

Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations).[82] Germ line DNA repair mutations are noted on the figure's left side. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.[83]

In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code for small RNAs called microRNAs (or miRNAs). MiRNAs do not code for proteins, but can "target" protein-coding genes and reduce their expression.

Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be "driver" mutations and the remaining ones may be "passenger" mutations.[84]

Metastasis is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize.[85] Most cancer deaths are due to cancer that has metastasized.[86]

Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.[85]

Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these lead to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

People may become extremely anxious and depressed post-diagnosis. The risk of suicide in people with cancer is approximately double the normal risk.[87]

Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:

Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ or tissue of origin as the root. For example, cancers of the liver parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma and a cancer arising from fat cells is called a liposarcoma. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the adjective ductal refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.

Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma.

Some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, spindle cell carcinoma and small-cell carcinoma.

The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of tissue tests. These tests may provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment.

Cancer prevention is defined as active measures to decrease cancer risk.[89] The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable.[90] Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.[91]

Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, insufficient diet, physical inactivity, alcohol, sexually transmitted infections and air pollution.[92] Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior.

While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive.[9][93] The primary dietary factors that increase risk are obesity and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion.[94][95] A 2014 meta-analysis find no relationship between fruits and vegetables and cancer.[96]Coffee is associated with a reduced risk of liver cancer.[97] Studies have linked excess consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures.[98][99] In 2015 the IARC reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers.[100][101]

Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains and fish and an avoidance of processed and red meat (beef, pork, lamb), animal fats and refined carbohydrates.[9][93]

Medications can be used to prevent cancer in a few circumstances.[102] In the general population, NSAIDs reduce the risk of colorectal cancer; however, due to cardiovascular and gastrointestinal side effects, they cause overall harm when used for prevention.[103]Aspirin has been found to reduce the risk of death from cancer by about 7%.[104]COX-2 inhibitors may decrease the rate of polyp formation in people with familial adenomatous polyposis; however, it is associated with the same adverse effects as NSAIDs.[105] Daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women.[106] The benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear.[107]

Vitamins are not effective at preventing cancer,[108] although low blood levels of vitamin D are correlated with increased cancer risk.[109][110] Whether this relationship is causal and vitamin D supplementation is protective is not determined.[111]Beta-carotene supplementation increases lung cancer rates in those who are high risk.[112]Folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps.[113] It is unclear if selenium supplementation has an effect.[114]

Vaccines have been developed that prevent infection by some carcinogenic viruses.[115]Human papillomavirus vaccine (Gardasil and Cervarix) decrease the risk of developing cervical cancer.[115] The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.[115] The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.[116]

Unlike diagnostic efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear.[117] This may involve physical examination, blood or urine tests or medical imaging.[117]

Cancer screening is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. Universal screening or mass screening involves screening everyone.[118]Selective screening identifies people who are at higher risk, such as people with a family history.[118] Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.[117] These factors include:

The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:

Screens for gastric cancer using photofluorography due to the high incidence there.[19]

Genetic testing for individuals at high-risk of certain cancers is recommended by unofficial groups.[116][132] Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.[132]

Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The treatment intent may or may not be curative.

Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites.[133] Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells.

Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML).[134] Currently, targeted therapies exist for breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.[135]

The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers.[136] Chemotherapy is curative for some cancers, such as some leukemias,[137][138] ineffective in some brain tumors,[139] and needless in others, such as most non-melanoma skin cancers.[140] The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.

Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve symptoms. It works by damaging the DNA of cancerous tissue, killing it. To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy.[141][142][143]

Radiation therapy is used in about half of cases. The radiation can be either from internal sources (brachytherapy) or external sources. The radiation is most commonly low energy x-rays for treating skin cancers, while higher energy x-rays are used for cancers within the body.[144] Radiation is typically used in addition to surgery and or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone.[145] For painful bone metastasis, it has been found to be effective in about 70% of patients.[145]

Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of definitive diagnosis and staging of tumors, as biopsies are usually required. In localized cancer, surgery typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the area. For some types of cancer this is sufficient to eliminate the cancer.[136]

Palliative care refers to treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve quality of life.

People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care.[146] This applies to patients who:[147]

Palliative care may be confused with hospice and therefore only indicated when people approach end of life. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed.

Multiple national medical guidelines recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.[148][149][150]

A variety of therapies using immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997. Approaches include antibodies, checkpoint therapy and adoptive cell transfer.[151]

Complementary and alternative cancer treatments are a diverse group of therapies, practices and products that are not part of conventional medicine.[152] "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine.[153] Most complementary and alternative medicines for cancer have not been studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, "The label 'unproven' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been 'disproven'."[154]

Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse. About half of patients receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from that cancer or its treatment.[19]

Survival is worse in the developing world,[19] partly because the types of cancer that are most common there are harder to treat than those associated with developed countries.[155]

Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed.[156] The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, partly due to treatment of the first cancer and to better compliance with screening.[156]

Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patient's age and overall health. Those who are frail with other health problems have lower survival rates than otherwise healthy people. Centenarians are unlikely to survive for five years even if treatment is successful. People who report a higher quality of life tend to survive longer.[157] People with lower quality of life may be affected by depression and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal.

Cancer patients have an increased risk of blood clots in veins. The use of heparin appears to improve survival and decrease the risk of blood clots.[158]

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Nanomedicine: Nanotechnology, Biology and Medicine …

Posted: October 20, 2016 at 1:45 am

Atomic force microscopy (AFM) was used here to study chronic myeloid leukemia (CML) stem cells in dormant (quiescent) and proliferating stages. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation seems to be a common cause of recurrence or relapse of CML. The collage shows a scheme of the AFM method and the found biophysical difference between these cells in the density of the pericellular layer surrounding cells.

This review gathers important and up-to-date information about variable synthetic methods that lead to attainment of magnetic nanoparticles with different shape and size. Moreover, information summarized within this manuscript determines the basics of sensing principles of magnetic nanoparticles. Furthermore here we report functionalization and modification of magnetic nanoobjects in order to achieve surfaces suitable for selective drug delivery, medical diagnosis and applications. Ultimately, one chapter is especially devoted to alternative green synthesis of nanoparticles.

Siderophores and oligopeptides take advantage of specific microbial active transport systems. Particular types of cell penetrating peptides, carbon nanotubes and terpenoid derivatives enter the cells by direct translocation. Dendrimers and large cell penetrating peptides are internalized by endocytosis. All these compounds conjugated with antimicrobials act as nanocarriers and transport the cargoes across the biomembranes. Once the conjugate is internalized, the active component could reach its intracellular target, either after release from the conjugate or in an intact form.

MPLA-coating of HBsAg nanocapsules (NCs) enhanced the uptake of NCs by neonatal and adult monocyte-derived dendritic cells (moDCs). The TLR4 mediated phagocytosis and the additional stimulation with IFN induced up-regulated expression levels of the co-stimulatory molecules CD80/86, the MHC II molecule, and the secretion of the pro-inflammatory cytokines TNF-, IL-12 and IL-6. Neonatal moDCs pulsed with MPLA-HBsAg-NCs plus IFN possessed the ability to trigger nave T cells towards TH1 immunity. The antigen-specific T cell proliferation was associated with the secretion of TH1 cell-specific IFN release.

A poly(phosphorhydrazone) dendrimer capped with amino-bis(methylene phosphonate) end groups enables the proliferation of human NK cells. This specific outcome results from a complex cross-talk between dendrimer-activated monocytes and autologous NK cells. During this crosstalk, dendrimer-activated monocytes are needed to enable the proliferation of NK cells, but ultimately, the NK cells have to kill autologous monocytes to proliferate. Like the yin and the yang, these cells have contrary but interdependent activities at the same time. This specific amplification of NK cells is also possible starting from peripheral blood of multiple myeloma patients, paving the road for NK cell-based anti-cancer immunotherapies.

The enzyme-responsive peptide drug conjugate specifically delivers the drug to prostate cancer cells. The PSA substrate is cleaved in the tumor interstitial space to release the dipeptide-linked TGX-D1, which enters the cells via overexpressed dipeptide transporters in prostate cancer cells. TGX-D1 is finally released from the dipeptide after cleavage of the ester linker inside the cells to exert its pharmacological effect. The intact peptidedrug conjugate may also enter the cells directly via endocytosis, and the ester bond can be cleaved inside the cells to release the active drug.

Overall properties and applications of synthesized magnetic nanoparticles coated by amphotericin B (red balls) or nystatin (blue balls) or their mixture against Candida cells.

Hydrophobic core protected graft copolymers (HC-PGC) such as MPEG-gPLL acylated with oleic acid, promote the formation of nanoparticles of water-insoluble benzophenone-uracyl non-nucleoside reverse transcriptase inhibitors after the co-lyophilization. These nanoparticles bind to the surface of HIV-1 infected effector cells and result in a high selectivity anti-HIV index because of their low toxicity.

Mice were fed with an MCD diet seven days ahead to develop NAFLD, and were then treated with saline, FNB crude drug or FNB-Nanolipo by gavage and meanwhile continuously fed with the MCD diet for another seven days. Compared to the FNB crude drug, the FNB-Nanolipo significantly enhanced oral absorption of FNB and therefore, significantly cured NAFLD induced by the MCD diet.

Iontophoresis for transcutaneous immunization using ovalbumin (OVA) as a model antigen, liposomes and silver nanoparticles (NPAg): in vitro iontophoresis of the liposomal dispersion containing NPAg improved OVA penetration into the viable epidermis, where antigen presenting cells are located. This increase in OVA skin penetration resulted in a humoral immune response similar to that obtained following a subcutaneous injection of OVA. The cellular immune responses that were obtained after iontophoresis of OVA-liposomes and OVA-liposomes w/o NPAg were more evident than those obtained after subcutaneous injection.

We show that polyethyleneimine/magnetic nanoparticles based delivery vector (PEI/MNP) is suitable for production of miRNA-modified endothelial cells in terms of efficiency and safety. The obtained transfected cells can be guided to the site of interest using a magnetic field and their fate can be noninvasively traced using magnetic resonance imaging. This multifunctional approach for transient cell modification bears particular interest as a basis for clinically relevant cell engineering.

The formation of folate targeted CD nanoparticles encapsulating RelA siRNA leads to specific folate mediated uptake in PSMA+ cells, the specific knockdown of RelA and an increase in the half-life of the siRNA

The improvement of osseointegration will be a great challenge for the design of the future generation of bone implants. The application of specific nanotopographies on the surface of bone implants is a potential strategy to achieve improved quality, without the need for changes of the implant design. In the current paper, nanogrooved topographies that were reproduced into epoxy resin cylinders could significantly increase bone regeneration around the implants in a rat femoral condyle model, compared to rough control surfaces.

Different from traditional idea, we designed and synthesized a highly hydrophobic reduction-sensitive docetxel prodrug with a disulfide bond inserted into the linker between docetaxel and vitamin E, which could self-assemble in water to form self-assembled nanoparticles without the help of surface active substances. Compared with a docetaxel Tween80-containing formulation, the unique nanomedicine had many advantages, including high drug payload, advanced stability, superior reproducibility, low toxicty, prolonged circulation and increased therapeutic efficacy. The highly reproducible self-assembled nanoparticles prepared by simple nanoprecipitation technology are more attractive and effective nanomedicines, and might be a promising nano-drug delivery system for other anticancer drug.

Currently, clinical ultrasonography and serum alpha-fetoprotein have limited specificity and sensitivity for the detection of hepatocellular carcinoma (HCC). In this study, based on Au@Ag NRs nanorods surface-enhanced Raman spectroscopy(SERS), we performed a label-free, non-invasive SERS test on 230 serum samples (47 HCC, 68 breast cancer, 55 lung cancer, and 60 normal control) to identify distinctive Raman spectrum peaks as a metabolic fingerprint to predict HCC. This paper is the first to report on the detection of serum metabolic profiles in HCC patients through SERS. In addition, this study is also the first to detect and compare serum SERS in three types of cancer to determine the general serum metabolic alterations among cancer patients. Furthermore, SERS combined with orthogonal partial least squares discriminant analysis exhibited good diagnostic performance for HCC, with the receiver operating characteristic curve having an area under curve value of 0.991. The present study provides new insights into the detection of metabolic processes related to the biology of HCC through Raman spectroscopy.

Radiotherapy is a key component of prostate cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic efficacy of radiotherapy. In this study, we engineered a nanoparticle formulation of Dbait, a new class of DNA damage repair inhibitor, with H1 (folatepolyethylenimine600cyclodextrin) nanopolymer. We demonstrated that H1/Dbait nanoparticle was a potent radiosensitizer in vitro and in vivo. Our study supports further investigations using nanoparticles to deliver DNA damage repair inhibitors to improve the therapeutic index of radiotherapy for prostate cancer.

Cerium oxide nanoparticles (20mg/kg) given intravenously twice a week prolonged survival in SOD1G93A transgenic mice. Treatment was started at the onset of muscle weakness at ~113days of age.

The hallmark of chronic obstructive lung diseases, such as COPD and CF, is intermittent or stable exacerbation that initiates progression of chronic inflammatory lung disease. Although, we have made significant progress in the development of anti-inflammatory drugs to treat these diseases but in order to provide sustained drug-delivery to target cells, there is a need for nano-carrier(s) that can circumvent obstructive airway defense. Hence, in this study we evaluated the efficacy of neutrophil-targeted nanoparticle in delivering non-steroidal anti-inflammatory drug, ibuprofen to control Pa-LPS induced inflammatory lung disease and cigarette smoke induced emphysema.

Subretinal injection of SP-PA-PRPF31 nanoparticles in heterozygous knock-in (KI) Prpf31A216P/+ mice. The retinal thickness measured by optical coherence tomography (OCT) in KI Prpf31A216P/+ mice treated with SP-PA-PRPF31nanoparticles was a similar value to wild type mice. These nanomedicines not only improved visual function but also retarded or reversed retinal degeneration in KI Prpf31A216P/+ mice, evidenced by the absence of retinal atrophy.

Gold nanorods (GNRs) inhibit respiratory syncytial virus (RSV) in vitro and in vivo. The antiviral gene expression study showed interplay of Toll-like receptor, NOD-like receptor and RIG-I-like receptor signaling pathways. Transmission electron microcopy, histological investigation and cytokine analysis indicate that GNRs stimulates innate immune response resulting in RSV inhibition.

This figure shows the formation of G4AcFaHSTK compact nanoparticles from the interaction between HSTK-based plasmids and partially acetylated, folic acid-conjugated, cationic 4th-generation polyamidoamine dendrimers (G4AcFa). Also, it shows the application of the real-time PFQNM mode of AFM to visualize the morphological and nanomechanical changes of individual live and dividing HeLa cells in their native environment upon their attack by G4AcFaHSTK.

After proper oral immunization schedules using SBA-15 as adjuvant, the recruitment of inflammatory cells to Peyers patches and mesenteric lymph nodes and the enhanced production of specific antibodies, as well as the non-influence of silica in the polarization to TH1 or TH2 immune responses, were shown.

Increased levels of soluble amyloid-beta (A) oligomers are suspected to underlie Alzheimer's disease (AD) pathophysiology through the formation of uncontrolled multi-subunit A pores in cellular membranes. In this study, the efficacy of small molecule NPT-440-1 modulation of A1-42 pore permeability was examined. We show that co-incubation of B103 rat neuronal cells with NPT-440-1 and A1-42 prevented calcium influx. In purified lipid bilayers, preincubation prior to membrane introduction was required to prevent conductance despite the presence of pore structures. The results point to compound-induced structural modulation leading to collapsed pores and suggest that pharmacological modulation of A1-42 could prevent AD pathogenesis.

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International Masters Program Molecular Medicine …

Posted: October 20, 2016 at 1:44 am

"One thing that was really great about the program was the combination of theory in the morning and practical work in the afternoon. This helped me keep everything in perspective and I found it highly motivating. In the lab I also learned so much; not only a lot of new techniques, but also how to approach and tackle a scientific question, and how to go about designing an experiment to specifically answer the question. Of course I had some idea about this before I began the program, but the lab placements enabled me to really practice this at a professional level. In my thesis right now, for example, I have a great deal of flexibility over the work Im doing, but I also have the chance to consistently check back with my supervisor to discuss next steps and possible future experiments. This combination of working independently but with support is essential for me to mature on the scientific level. In all, it also gives me the feeling that I am a researcher and not just another student."

Radwa Sharaf, graduate 2013, pursuing her PhD at Harvard soon.

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International Masters Program Molecular Medicine ...

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Molecular Medicine – Wake Forest Baptist Health

Posted: October 20, 2016 at 1:44 am

From its home within the Department of Internal Medicine Section on Molecular Medicine, the Molecular Medicine and Translational Science program trains PhD students in research to better understand human diseases at a molecular level and translate that knowledge to improved diagnostics, treatment, and disease prevention. The MMTS program includes scientists from all major basic science and clinical programs at Wake Forest University and was one of the first established molecular medicine programs nationwide. Beginning in 2011, MMTS joined four other complementary PhD programs in the Wake Forest University Graduate Schools Molecular and Cellular Biosciences track, where combined expertise will be utilized to enhance the depth of student learning and discovery.

To learn more about the MMTS degree programs and their requirements, or aboutthe program's accomplished faculty, please follow the links on the left.

Program Directors and Contacts

Director: John S. Parks, PhD,Professor Department of Internal Medicine Molecular Medicine Phone: 336-716-2145 Email:jparks@wakehealth.edu

Co-Director: Robert N. Taylor, MD, PhD, Professor Department of Obstetrics and Gynecology Phone: 336-716-5451 Email: rtaylor@wakehealth.edu

Program Recruiter: Michael C. Seeds, PhD, Assistant Professor Department of Internal Medicine - Molecular Medicine Phone: 336-713-4259 E-mail: mseeds@wakehealth.edu

MMTS Policies and Procedures

MMTS Graduate Program Faculty

Molecular Medicine Journal Club

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Molecular Medicine - Wake Forest Baptist Health

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Cellular and Molecular Medicine Graduate Program

Posted: October 20, 2016 at 1:44 am

The Graduate Training Program in Cellular and Molecular Medicine prepares scientists for laboratory research at the cellular and molecular level with a direct impact on the understanding, diagnosis, treatment and prevention of human diseases. The Ph.D. graduates of the Program will have a rigorous training in scientific research and a thorough knowledge of human biology and human diseases.

The CMM program grew out of a need for training at the interface between medicine and the traditional basic science disciplines. Rapid progress in cellular and molecular biology has strongly impacted clinical medicine, offering insights on fundamental causes of many diseases. Now new discoveries in the laboratory can be applied rapidly to the diagnosis, treatment and prevention of disease. This has been made possible by emerging technology that allows scientists to identify genetic and molecular defects causing or predisposing to disease. The trainees in this program are working precisely at this interface between science and medicine where they will be able to contribute to the long term well being of society.

Johns Hopkins University School of Medicine supports state of the art research and animal facilities, all on the East Baltimore campus.

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Cellular and Molecular Medicine Graduate Program

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Home – Weatherall Institute of Molecular Medicine

Posted: October 20, 2016 at 1:44 am

The mission of the MRC Weatherall Institute of Molecular Medicine (WIMM) is to undertake internationally competitive research into the processes underlying normal cell and molecular biology and to determine the mechanisms by which these processes are perturbed in inherited and acquired human diseases. It is also our mission to translate this research to improve human health. The WIMM is uniquely placed among biomedical institutes throughout the world in its pioneering vision of combining outstanding clinical research with excellent basic science. The WIMM Faculty currently includes an equal mixture of scientists and clinicians working together and in collaboration with the National Institute of Health Research, the NHS and commercial companies with the aim of improving the diagnosis and treatment of human diseases. The major topics of current research include haematology, immunology, stem cell biology, oncology and inherited human genetic diseases. The Institute benefits from strategic support from the MRC.

The Institute values communication with members of the broader scientific community and the general public and with the support of the Medical Research Council (MRC) we have commissioned three short videos to explain our mission.

This month, Dr Iztok Urbani joined Christian Eggeling's lab in the MRC Human Immunology Unit, supported by a prestigious Marie Skodowska-Curie postdoctoral fellowship. Iztok completed his studies in physics in 2009 at the University of Ljubljana, Slovenia, and obtained his PhD in biophysics in 2013 from the University of Maribor, Slovenia. During his 2-year fellowship here at the MRC WIMM, he will work on further improving super-resolution ...

The Lister Institute was founded in 1891 as a research institute researching vaccines and antitoxins, and over its impressive 125-year history has developed into one of the most prestigious funders of scientific research in the UK. Scientists supported by the Lister Institute have been involved in some of the most pivotal scientific and medical discoveries over the past century, including development of the UKs first diphtheria vaccine, ...

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We are seeking to appoint a Junior Group Leader in Computational Biology and Bioinformatics within the Human Immunology Unit (HIU), Investigative Medicine at the Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford (www.imm.ox.ac.uk/mrc-human-immunology-unit). Reporting to the Director of the HIU you will be required to add value to the ongoing programmes within the Unit as well as establish your own programme as Junior ...

Other Vacancies

Seeing is believing: what does your DNA look like in3D?

Clue: its a bit more complicated than a bendy ladder. Over the past year, scientists working in the Computational Biology Research Group and the MRC Molecular Haematology Unit at the MRC WIMM have been collaborating with Goldsmiths University in London to produce CSynth: new interactive software which allows users to visualize DNA structures in three dimensions. The team took the technology to New Scientist Live in September this year, and wowed hundreds of people with this incredible new tool. In this blog post, Bryony Graham describes the science behind the technology, and how the team managed to explain some pretty complex genomics to thousands of people using some pieces of string, a few fluffy blood cells and a couple of touchscreens, all whilst working under a giant inflatable E. coli suspended from the ceiling. Of course.

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Home - Weatherall Institute of Molecular Medicine

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Molecular Genetics – DNA, RNA, & Protein

Posted: October 20, 2016 at 1:44 am

MOLECULAR GENETICS You Are Here* molecular basis of inheritance Genes ---> Enzymes ---> Metabolism (phenotype) Central Dogma of Molecular Biology* DNA -transcription-->RNA-translation--> Protein Concept Activity -17.1 Overview of Protein Synthesis - INFORMATION FLOW

What is a GENE = ? DNA is the genetic material... [ but what about, retroviruses, as HIV & TMV, contain RNA ] - a discrete piece of deoxyribonucleic acid - linear polymer of repeating nucleotide monomers nucleotides* --> A adenine,C cytosine T thymidine,G guanine --> polynucleotide*

Technology with a Twist - Understanding Genetics

INFORMATION PROCESSING & the CENTRAL DOGMA - the letters of the genetic alphabet... are the nucleotides A, T, G, & C of DNA - the unit of information is CODON = genetic 'word' a triplet sequence of nucleotides 'CAT' in a polynucleotide 3 nucleotides = 1 codon (word) = 1 amino acid in a polypeptide - the definition of (codon) word = amino acid - Size of Human Genome: 3,000,000,000 base pairs or 1.5b in single strand of DNA genes 500,000,000 possible codons (words or amino acids) - average page your textbook = approx 850 words thus, human genome is equal to 588,000 pages or 470 copies of bio text book reading at 3 bases/sec it would take you about 47.6 years @ 8h/d - 7d/w WOW... extreme nanotechnology Mice & humans (indeed, most or all mammals including dogs, cats, rabbits, monkeys, & apes) have roughly the same number of nucleotides in their genomes -- about 3 billion bp. It is estimated that 99.9% of the 3billion n's of human genome is same person to person.

Experimental Proof of DNA as Genetic Material...

1. Transformation Experiments of Fred Griffith... (1920's) Streptococcus pneumoniae -pathogenic S strain & benign R transforming 'principle'* (converting R to S cells) is the genetic element 2. Oswald Avery, Colin MacLeod, & Maclyn McCarty... (1940's) suggest the transforming substance* is DNAmolecules, but... 3. Alfred Hershey & Martha Chase's* 1952 bacteriophage experiments*... VIRAL REPLICATION*[ phage infection & & lytic/lysogenic* ] a genetically controlled biological activity (viral reproduction) they did novel experiment... 1st real use radioisotopes in biology* CONCLUSION - DNA is genetic material because (32P) nucleic acid not (35S) protein guides* viral replication Sumanas, Inc. animation - Lifecycle of HIV virus

Structure of DNA ..... Discovery of Double Helix... Watson's book Nobel prize* -JD Watson, Francis Crick,Maurice Wilkins, but [ Erwin Chargaff & RosyFranklin]... Race for the Double Helix "Life Story" - a BBC dramatization of the discovery of DNA. used two approaches to decipher structure: 1. model building - figure* (are the bases in/out; are the sugar-P's in/out?) 2. x-ray diffraction*pattern* favor a DNA helix of constant diameter* we know now: DNA is a double stranded, helical, polynucleotide chains, made of... 4 nucleotides - A, T, G, C (purine & pyrimidines) in 2 polynucleotide strands (polymer chains) head-tail polarity [5'-----3'] - strands run antiparallel held together via weak H-Bonds & complimentary pairing - Chargaff's rule*..... A:T G:C A + G / T + C = 1.0 Fig's:sugar-P backbone*,base*pairing, dimensions*, models of DNA structure* john kyrk's animation of DNA & Quicktime movie of DNA structure literature references & myDNAi timeline*

Replication of DNA... (Arthur Kornberg - 1959 Nobel - died 10/26/07) copying of DNA into DNA is structurally obvious??? [figure*] Patterns of Replication* = conservative, semi-conservative, & dispersive Matt Meselson & Frank Stahl1958 - experimental design* can we separate 15N-DNA from 14N-DNA - (OLD DNA from NEW DNA)? sedimentation of DNA's (sucrose gradients --> CsCl gradients* & picture*) we can predict results... figure* & overview& all possible results Sumanas, Inc. animation - Meselson-Stahl DNA Replications*

Model of Replication is bacterial with DNA polymerase III... several enzymes* form a Replication Complex (Replisome) & include: helicase - untwists DNA topoisomerase [DNA gyrase] - removes supercoils, single strand binding proteins - stabilize replication fork, Primase - makes RNA primer POL III - synthesizes new DNA strands DNA polymerase I - removes RNA primer 1 base at a time, adds DNA bases DNA ligase repairs Okazaki fragments (seals lagging strand 3' open holes) Concept Activity - DNA Replication Review Structure of DNA polymerase III* copies both strands simultaneously, as DNA is Threaded Through a Replisome* a "replication machine", which may be stationary by anchoring in nuclear matrix Continuous & Discontinuous replication occur simultaneously in both strands

EVENTS: 1. DNA pol III binds at the origin of replication site in the template strand 2. DNA is unwound by replisome complex using helicase & topoisomerase 3. all polymerases require a preexisting DNA strand (PRIMER) to start replication, thus Primase adds a single short primer to the LEADING strand and adds many primers to the LAGGING strand 4. DNA pol III is a dimer adding new nucleotides to both strands primers direction of reading is 3' ---> 5' on template direction of synthesis of new strand is 5" ---> 3' rate of synthesis is substantial 400 nucleotide/sec 5. DNA pol I removes primer at 5' end replacing with DNA bases, leaves 3' hole 6. DNA ligase seals 3' holes of Okazaki fragments on lagging strand the sequence of events in detail* and DNA Repair* Rates of DNA synthesis: myDNAi movie of replication* native polymerase: 400 bases/sec with 1 error per 109 bases artificial: phophoramidite method (Marvin Caruthers, U.Colorado); ssDNA synthesis on polystyrene bead @ 1 base/300 sec with error rate of 1/100b

GENE Expression the Central Dogma of Molecular Biology depicts flow of genetic information Transcription - copying of DNA sequence into RNA Translation- copying of RNA sequence into protein DNA sequence -------> RNA sequence -----> amino acid sequence TAC AUG MET triplet sequence in DNA --> codon in mRNA ---->amino acid in protein Information : triplet sequence in DNA is the genetic word [codon] Compare Events: Procaryotes* vs. Eucaryotes* = Separation of labor Differences DNA vs. RNA (bases & sugars) and its single stranded Flow of Gene Information (FIG*) - One Gene - One enzyme (Beadle & Tatum) 18.3-Overview: Control of Gene Expression

Transcription - RNA polymerase Concept Activity 17.2 - Transcription RNA*polymerase - in bacteria Sigma factor* binds promoter & initiates* copying* [pnpase] transcription factors* are needed to recognize specific DNA sequence [motif*], binds to promoter DNA region [ activators & transcription factors*]* makes a complimentary copy* of one of the two DNA strands[sense strand] Quicktime movie of transcription*myDNAi Roger Kornberg's movie of transcription (2006 Nobel)* Kinds of RNA [table*] tRNA - small, 80n, anticodon sequence, single strand with 2ndary structure* function = picks up aa & transports it to ribosome rRNA - 3 individual pieces of RNA - make up the organelle = RIBOSOME primary transcript is processed into the 3 pieces of rRNA pieces(picture*) & recall structure of ribosome

Other classes of RNA: small nuclear RNA (snRNP's)- plays a structural and catalytic role in spliceosome* there are 5 snRNP's making a spliceosome [U1, U2, U4, U5, & U6]; they and participate in several RNA-RNA and RNA-protein interactions

SRP (signal recognition particle) - srpRNA is a component of the protein-RNA complex that recognizes the signal sequence of polypeptides targeted to the ER - figure*

small nucleolar RNA (snoRNA) - aids in processing of pre-rRNA transcripts for ribosome subunit formation in the nucleolus

micro RNA's (micro-RNA)- also called antisense RNA & interfereing RNA; c7-fig 19.9 short (20-24 nucleotide) RNAs that bind to mRNA inhibiting it. figure* present in MODEL eukaryotic organisms as:roundworms, fruit flies, mice, humans, & plants (arabidopsis); seems to help regulate gene expression by controlling the timing of developmental events via mRNA action also inhibits translation of target mRNAs. ex: siRNA --> [BARR Body*]

TRANSLATION - Making a Protein process of making a protein in a specific amino acid sequence from a unique mRNA sequence...[ E.M. picture* ] polypeptides are built on the ribosome (pic) on a polysome [ animation*] Sequence of 4 Steps in Translation... [glossary] 1. add an amino acid to tRNA -- > aa-tRNA - ACTIVATION* 2. assemble players [ribosome*, mRNA, aa-tRNA] - INITIATION* 3. adding new aa's via peptidyl transferase - ELONGATION* 4. stopping the process - TERMINATION* Concept CD Activity - 17.4 Events in Translation Review the processes - initiation, elongation, & termination myDNAi real-time movie of translation*& Quicktime movie of translation Review figures & parts: Summary fig* [ components, locations, AA-site, & advanced animation ] [ Nobel Committee static animations of Central Dogma ]

GENETIC CODE... ...is the sequence of nucleotides in DNA, but routinely shown as a mRNA code* ...specifies sequence of amino acids to be linked into the protein coding ratio* - # of n's... how many nucleotides specify 1 aa 1n = 4 singlets, 2n= 16 doublets, 3n = 64 triplets Student CD Activity - 11.2 - Triplet Coding S. Ochoa (1959 Nobel) - polynucleotide phosphorylase can make SYNTHETIC mRNA Np-Np-Np-Np <----> Np-Np-Np + Np Marshall Nirenberg (1968 Nobel)- synthetic mRNA's used in an in vitro system 5'-UUU-3' = pheU + C --> UUU, UUC, UCC, CCC UCU, CUC, CCU, CUU the Genetic CODE* - 64 triplet codons [61 = aa & 3 stop codons] universal (but some anomalies), 1 initiator codon (AUG), redundant but non-ambiguous, and exhibits "wobble*".

GENETIC CHANGE - a change in DNA nucleotide sequence (= change in mRNA) - 2 significant waysmutation & recombination [glossary] 1. MUTATION - a permanent change in an organism's DNA*that results in a different codon = different amino acid sequence Point mutation* - a single to few nucleotides change... - deletions, insertions, frame-shift mutations* [CAT] - single nucleotide base substitutions* : non-sense = change to no amino acid (a STOP codon) UCA --> UAA ser to non mis-sense = different amino acid UCA --> UUA ser to leu Sickle Cell Anemia* - a mis-sense mutation... (SCA-pleiotropy) another point mutation blood disease - thalassemia - Effects = no effect, detrimental (lethal), +/- functionality, beneficial

2. Recombination (Recombinant DNA)newly combined DNA's that [glossary]* can change genotype via insertion of NEW (foreign) DNA molecules into recipient cell 1. fertilization*- sperm inserted into recipient egg cell* --> zygote [n + n = 2n] 2. exchange of homologous chromatids via crossing over* = new gene combo's 3. transformation* - absorption of 'foreign' DNA by recipient cells changes cell 4. BACTERIAL CONJUGATION* - involves DNA plasmidsg* (F+ & R = resistance) conjugation may be a primitive sex-like reproduction in bacteria[Hfr*] 5. VIRAL TRANSDUCTION - insertion via a viral vector(lysogeny* &TRANSDUCTION*) general transduction - pieces of bacterial DNA are packaged w viral DNA during viral replication restricted transduction - a temperate phage goes lytic carrying adjacent bacterial DNA into virus particle 6. DESIGNER GENES - man-made recombinant DNA molecules

Designer Genes - Genetic Engineering - Biotechnology

RECOMBINANT DNA TECHNOLOGY... a collection of experimental techniques, which allow for isolation, copying, & insertion of new DNA sequences into host-recipientcells by A NUMBER OF laboratory protocols & methodologies

Restriction Endonucleases-[glossary]*... diplotomic cuts (unequal) at uniqueDNA sequences Eco-R1-figure* @ mostly palindromes... [never odd or even] 5' GAATTC 3' 5' G. . . . . + AATTC 3' 3' CTTAAG 5' 3' CTTAA .. .. G 5' campbell 7/e movie* DNA's cut this way have STICKY (complimentary) ENDS & can be reannealed or spliced* w other DNA molecules to produce new genes combosand sealed via DNA ligase. myDNAi movie of restriction enzyme action*

Procedures of Biotechnology? [Genome Biology Research] A. Technology involved in Cloning a Gene...[animation* & the tools of genetic analysis] making copies of gene DNA 1. via a plasmid*[ A.E. fig& human shotgun plasmid cloning & My DNAi movie*] 2. Librariesg... [ library figure* & BAC's* &Sumanas animation - DNA fingerprint library] 3. Probesg... [ cDNAg & reverse transcriptaseg & DNA Probe Hybridizationg... cDNA figure*& cDNA library* & a probe for a gene of interest* finding a gene with a probe among a library*] 4. Polymerase Chain Reactiong & figure 20.7* & animation*+Sumanas, Inc. animation* the PCR song PCR reaction protocol & Xeroxing DNA & Taq polymerase

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Molecular Genetics - DNA, RNA, & Protein

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Alternative medicine – Wikipedia, the free encyclopedia

Posted: October 20, 2016 at 1:44 am

Alternative or fringe medicine is any practice claimed to have the healing effects of medicine and is: proven not to work; has no scientific evidence showing that it works; or that is solely harmful.[n 1][n 2][n 3] Alternative medicine is not a part of medicine,[n 1][n 4][n 5][n 6] or science-based healthcare systems.[1][2][4] It consists of a wide variety of practices, products, and therapiesranging from those that are biologically plausible but not well tested, to those with known harmful and toxic effects.[n 4][5][6][7][8][9] Despite significant costs in testing alternative medicine, including $2.5 billion spent by the United States government, almost none have shown any effectiveness beyond that of false treatments (placebo).[10][11] Perceived effects of alternative medicine are caused by the placebo effect, decreased effects of functional treatment (and thus also decreased side-effects), and regression toward the mean where spontaneous improvement is credited to alternative therapies.

Complementary medicine or integrative medicine is when alternative medicine is used together with functional medical treatment, in a belief that it "complements" (improves the efficacy of) the treatment.[n 7][13][14][15][16] However, significant drug interactions caused by alternative therapies may instead negatively influence the treatment, making treatments less effective, notably cancer therapy.[17][18]CAM is an abbreviation of complementary and alternative medicine.[19][20] It has also be called sCAM or SCAM for "so-called complementary and alternative medicine" or "supplements and complementary and alternative medicine".[21][22]Holistic health or holistic medicine claims to take into account the "whole" person, including spirituality in its treatmentsand is a similar concept. Due to its many names the field has been criticized for intense rebranding of what are essentially the same practices: as soon as one name is declared synonymous with quackery, a new is chosen.

Alternative medical diagnoses and treatments are not included in the science-based treatments taught in medical schools, and are not used in medical practice where treatments are based on scientific knowledge. Alternative therapies are either unproven, disproved, or impossible to prove,[n 8][5][13][24][25] and are often based on religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, or fraud.[5][26][6][13] Regulation and licensing of alternative medicine and health care providers varies between and within countries. Marketing alternative therapies as treating or preventing cancer is illegal in many countries including the United States and most parts of the European Union.

Alternative medicine has been criticized for being based on misleading statements, quackery, pseudoscience, antiscience, fraud, or poor scientific methodology. Promoting alternative medicine has been called dangerous and unethical.[n 9][28] Testing alternative medicine that have no scientific basis has been called a waste of scarce medical research resources.[29][30] Critics have said "there is really no such thing as alternative medicine, just medicine that works and medicine that doesn't",[31] and the problem is not only that it does not work, but that the "underlying logic is magical, childish or downright absurd".[32] There have also been calls that the concept of any alternative medicine that works is paradoxical, as any treatment proven to work is simply "medicine".[33]

Alternative medicine consists of a wide range of health care practices, products, and therapies. The shared feature is a claim to heal that is not based on the scientific method. Alternative medicine practices are diverse in their foundations and methodologies.[1] Alternative medicine practices may be classified by their cultural origins or by the types of beliefs upon which they are based.[5][26][1][13] Methods may incorporate or be based on traditional medicinal practices of a particular culture, folk knowledge, supersition, spiritual beliefs, belief in supernatural energies (antiscience), pseudoscience, errors in reasoning, propaganda, fraud, new or different concepts of health and disease, and any bases other than being proven by scientific methods.[5][26][6][13] Different cultures may have their own unique traditional or belief based practices developed recently or over thousands of years, and specific practices or entire systems of practices.

Alternative medicine, such as using naturopathy or homeopathy in place of conventional medicine, is based on belief systems not grounded in science.[1]

Homeopathy is a system developed in a belief that a substance that causes the symptoms of a disease in healthy people cures similar symptoms in sick people.[n 10] It was developed before knowledge of atoms and molecules, and of basic chemistry, which shows that repeated dilution as practiced in homeopathy produces only water, and that homeopathy is scientifically implausible.[36][37][38][39] Homeopathy is considered quackery in the medical community.[40]

Naturopathic medicine is based on a belief that the body heals itself using a supernatural vital energy that guides bodily processes,[41] a view in conflict with the paradigm of evidence-based medicine.[42] Many naturopaths have opposed vaccination,[43] and "scientific evidence does not support claims that naturopathic medicine can cure cancer or any other disease".[44]

Alternative medical systems may be based on traditional medicine practices, such as traditional Chinese medicine, Ayurveda in India, or practices of other cultures around the world.[1]

Traditional Chinese medicine is a combination of traditional practices and beliefs developed over thousands of years in China, together with modifications made by the Communist party. Common practices include herbal medicine, acupuncture (insertion of needles in the body at specified points), massage (Tui na), exercise (qigong), and dietary therapy. The practices are based on belief in a supernatural energy called qi, considerations of Chinese Astrology and Chinese numerology, traditional use of herbs and other substances found in Chinaa belief that the tongue contains a map of the body that reflects changes in the body, and an incorrect model of the anatomy and physiology of internal organs.[5][45][46][47][48][49]

The Chinese Communist Party Chairman Mao Zedong, in response to a lack of modern medical practitioners, revived acupuncture, and had its theory rewritten to adhere to the political, economic, and logistic necessities of providing for the medical needs of China's population.[50][pageneeded] In the 1950s the "history" and theory of traditional Chinese medicine was rewritten as communist propaganda, at Mao's insistence, to correct the supposed "bourgeois thought of Western doctors of medicine".Acupuncture gained attention in the United States when President Richard Nixon visited China in 1972, and the delegation was shown a patient undergoing major surgery while fully awake, ostensibly receiving acupuncture rather than anesthesia. Later it was found that the patients selected for the surgery had both a high pain tolerance and received heavy indoctrination before the operation; these demonstration cases were also frequently receiving morphine surreptitiously through an intravenous drip that observers were told contained only fluids and nutrients.[45]Cochrane reviews found acupuncture is not effective for a wide range of conditions.[52] A systematic review of systematic reviews found that for reducing pain, real acupuncture was no better than sham acupuncture.[53] Although, other reviews have found that acupuncture is successful at reducing chronic pain, where as sham acupuncture was not found to be better than a placebo as well as no-acupuncture groups.[54]

Ayurvedic medicine is a traditional medicine of India. Ayurveda believes in the existence of three elemental substances, the doshas (called Vata, Pitta and Kapha), and states that a balance of the doshas results in health, while imbalance results in disease. Such disease-inducing imbalances can be adjusted and balanced using traditional herbs, minerals and heavy metals. Ayurveda stresses the use of plant-based medicines and treatments, with some animal products, and added minerals, including sulfur, arsenic, lead, copper sulfate.[citation needed]

Safety concerns have been raised about Ayurveda, with two U.S. studies finding about 20 percent of Ayurvedic Indian-manufactured patent medicines contained toxic levels of heavy metals such as lead, mercury and arsenic. Other concerns include the use of herbs containing toxic compounds and the lack of quality control in Ayurvedic facilities. Incidents of heavy metal poisoning have been attributed to the use of these compounds in the United States.[8][57][58][59]

Bases of belief may include belief in existence of supernatural energies undetected by the science of physics, as in biofields, or in belief in properties of the energies of physics that are inconsistent with the laws of physics, as in energy medicine.[1]

Biofield therapies are intended to influence energy fields that, it is purported, surround and penetrate the body.[1] Writers such as noted astrophysicist and advocate of skeptical thinking (Scientific skepticism) Carl Sagan (1934-1996) have described the lack of empirical evidence to support the existence of the putative energy fields on which these therapies are predicated.

Acupuncture is a component of traditional Chinese medicine. Proponents of acupuncture believe that a supernatural energy called qi flows through the universe and through the body, and helps propel the bloodand that blockage of this energy leads to disease.[46] They believe that inserting needles in various parts of the body, determined by astrological calculations, can restore balance to the blocked flows and thereby cure disease.[46]

Chiropractic was developed in the belief that manipulating the spine affects the flow of a supernatural vital energy and thereby affects health and disease.

In the western version of Japanese Reiki, practitioners place their palms on the patient near Chakras that they believe are centers of supernatural energies, and believe that these supernatural energies can transfer from the practitioner's palms to heal the patient.

Bioelectromagnetic-based therapies use verifiable electromagnetic fields, such as pulsed fields, alternating-current, or direct-current fields in an unconventional manner.[1]Magnetic healing does not claim existence of supernatural energies, but asserts that magnets can be used to defy the laws of physics to influence health and disease.

Mind-body medicine takes a holistic approach to health that explores the interconnection between the mind, body, and spirit. It works under the premise that the mind can affect "bodily functions and symptoms".[1] Mind body medicines includes healing claims made in yoga, meditation, deep-breathing exercises, guided imagery, hypnotherapy, progressive relaxation, qi gong, and tai chi.[1]

Yoga, a method of traditional stretches, exercises, and meditations in Hinduism, may also be classified as an energy medicine insofar as its healing effects are believed to be due to a healing "life energy" that is absorbed into the body through the breath, and is thereby believed to treat a wide variety of illnesses and complaints.[61]

Since the 1990s, tai chi (t'ai chi ch'uan) classes that purely emphasise health have become popular in hospitals, clinics, as well as community and senior centers. This has occurred as the baby boomers generation has aged and the art's reputation as a low-stress training method for seniors has become better known.[62][63] There has been some divergence between those that say they practice t'ai chi ch'uan primarily for self-defence, those that practice it for its aesthetic appeal (see wushu below), and those that are more interested in its benefits to physical and mental health.

Qigong, chi kung, or chi gung, is a practice of aligning body, breath, and mind for health, meditation, and martial arts training. With roots in traditional Chinese medicine, philosophy, and martial arts, qigong is traditionally viewed as a practice to cultivate and balance qi (chi) or what has been translated as "life energy".[64]

Substance based practices use substances found in nature such as herbs, foods, non-vitamin supplements and megavitamins, animal and fungal products, and minerals, including use of these products in traditional medical practices that may also incorporate other methods.[1][11][65] Examples include healing claims for nonvitamin supplements, fish oil, Omega-3 fatty acid, glucosamine, echinacea, flaxseed oil, and ginseng.[66]Herbal medicine, or phytotherapy, includes not just the use of plant products, but may also include the use of animal and mineral products.[11] It is among the most commercially successful branches of alternative medicine, and includes the tablets, powders and elixirs that are sold as "nutritional supplements".[11] Only a very small percentage of these have been shown to have any efficacy, and there is little regulation as to standards and safety of their contents.[11] This may include use of known toxic substances, such as use of the poison lead in traditional Chinese medicine.[66]

Manipulative and body-based practices feature the manipulation or movement of body parts, such as is done in bodywork and chiropractic manipulation.

Osteopathic manipulative medicine, also known as osteopathic manipulative treatment, is a core set of techniques of osteopathy and osteopathic medicine distinguishing these fields from mainstream medicine.[67]

Religion based healing practices, such as use of prayer and the laying of hands in Christian faith healing, and shamanism, rely on belief in divine or spiritual intervention for healing.

Shamanism is a practice of many cultures around the world, in which a practitioner reaches an altered states of consciousness in order to encounter and interact with the spirit world or channel supernatural energies in the belief they can heal.[68]

Some alternative medicine practices may be based on pseudoscience, ignorance, or flawed reasoning.[69] This can lead to fraud.[5]

Practitioners of electricity and magnetism based healing methods may deliberately exploit a patient's ignorance of physics to defraud them.[13]

"Alternative medicine" is a loosely defined set of products, practices, and theories that are believed or perceived by their users to have the healing effects of medicine,[n 2][n 4] but whose effectiveness has not been clearly established using scientific methods,[n 2][n 3][5][6][23][25] whose theory and practice is not part of biomedicine,[n 4][n 1][n 5][n 6] or whose theories or practices are directly contradicted by scientific evidence or scientific principles used in biomedicine.[5][26][6] "Biomedicine" is that part of medical science that applies principles of biology, physiology, molecular biology, biophysics, and other natural sciences to clinical practice, using scientific methods to establish the effectiveness of that practice. Alternative medicine is a diverse group of medical and health care systems, practices, and products that originate outside of biomedicine,[n 1] are not considered part of biomedicine,[1] are not widely used by the biomedical healthcare professions,[74] and are not taught as skills practiced in biomedicine.[74] Unlike biomedicine,[n 1] an alternative medicine product or practice does not originate from the sciences or from using scientific methodology, but may instead be based on testimonials, religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources.[n 3][5][6][13] The expression "alternative medicine" refers to a diverse range of related and unrelated products, practices, and theories, originating from widely varying sources, cultures, theories, and belief systems, and ranging from biologically plausible practices and products and practices with some evidence, to practices and theories that are directly contradicted by basic science or clear evidence, and products that have proven to be ineffective or even toxic and harmful.[n 4][7][8]

Alternative medicine, complementary medicine, holistic medicine, natural medicine, unorthodox medicine, fringe medicine, unconventional medicine, and new age medicine are used interchangeably as having the same meaning (are synonyms) in some contexts,[75][76][77] but may have different meanings in other contexts, for example, unorthodox medicine may refer to biomedicine that is different from what is commonly practiced, and fringe medicine may refer to biomedicine that is based on fringe science, which may be scientifically valid but is not mainstream.

The meaning of the term "alternative" in the expression "alternative medicine", is not that it is an actual effective alternative to medical science, although some alternative medicine promoters may use the loose terminology to give the appearance of effectiveness.[5]Marcia Angell stated that "alternative medicine" is "a new name for snake oil. There's medicine that works and medicine that doesn't work."[78] Loose terminology may also be used to suggest meaning that a dichotomy exists when it does not, e.g., the use of the expressions "western medicine" and "eastern medicine" to suggest that the difference is a cultural difference between the Asiatic east and the European west, rather than that the difference is between evidence-based medicine and treatments that don't work.[5]

"Complementary medicine" refers to use of alternative medical treatments alongside conventional medicine, in the belief that it increases the effectiveness of the science-based medicine.[79][80][81] An example of "complementary medicine" is use of acupuncture (sticking needles in the body to influence the flow of a supernatural energy), along with using science-based medicine, in the belief that the acupuncture increases the effectiveness or "complements" the science-based medicine.[81] "CAM" is an abbreviation for "complementary and alternative medicine".

The expression "Integrative medicine" (or "integrated medicine") is used in two different ways. One use refers to a belief that medicine based on science can be "integrated" with practices that are not. Another use refers only to a combination of alternative medical treatments with conventional treatments that have some scientific proof of efficacy, in which case it is identical with CAM.[16] "holistic medicine" (or holistic health) is an alternative medicine practice that claims to treat the "whole person" and not just the illness.

"Traditional medicine" and "folk medicine" refer to prescientific practices of a culture, not to what is traditionally practiced in cultures where medical science dominates. "Eastern medicine" typically refers to prescientific traditional medicines of Asia. "Western medicine", when referring to modern practice, typically refers to medical science, and not to alternative medicines practiced in the west (Europe and the Americas). "Western medicine", "biomedicine", "mainstream medicine", "medical science", "science-based medicine", "evidence-based medicine", "conventional medicine", "standard medicine", "orthodox medicine", "allopathic medicine", "dominant health system", and "medicine", are sometimes used interchangeably as having the same meaning, when contrasted with alternative medicine, but these terms may have different meanings in some contexts, e.g., some practices in medical science are not supported by rigorous scientific testing so "medical science" is not strictly identical with "science-based medicine", and "standard medical care" may refer to "best practice" when contrasted with other biomedicine that is less used or less recommended.[n 11][84]

Prominent members of the science[31][85] and biomedical science community[24] assert that it is not meaningful to define an alternative medicine that is separate from a conventional medicine, that the expressions "conventional medicine", "alternative medicine", "complementary medicine", "integrative medicine", and "holistic medicine" do not refer to anything at all.[24][31][85][86] Their criticisms of trying to make such artificial definitions include: "There's no such thing as conventional or alternative or complementary or integrative or holistic medicine. There's only medicine that works and medicine that doesn't;"[24][31][85] "By definition, alternative medicine has either not been proved to work, or been proved not to work. You know what they call alternative medicine that's been proved to work? Medicine;"[33] "There cannot be two kinds of medicine conventional and alternative. There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work. Once a treatment has been tested rigorously, it no longer matters whether it was considered alternative at the outset. If it is found to be reasonably safe and effective, it will be accepted;"[24] and "There is no alternative medicine. There is only scientifically proven, evidence-based medicine supported by solid data or unproven medicine, for which scientific evidence is lacking."[86]

Others in both the biomedical and CAM communities point out that CAM cannot be precisely defined because of the diversity of theories and practices it includes, and because the boundaries between CAM and biomedicine overlap, are porous, and change. The expression "complementary and alternative medicine" (CAM) resists easy definition because the health systems and practices it refers to are diffuse, and its boundaries poorly defined.[7][n 12] Healthcare practices categorized as alternative may differ in their historical origin, theoretical basis, diagnostic technique, therapeutic practice and in their relationship to the medical mainstream. Some alternative therapies, including traditional Chinese medicine (TCM) and Ayurveda, have antique origins in East or South Asia and are entirely alternative medical systems;[91] others, such as homeopathy and chiropractic, have origins in Europe or the United States and emerged in the eighteenth and nineteenth centuries. Some, such as osteopathy and chiropractic, employ manipulative physical methods of treatment; others, such as meditation and prayer, are based on mind-body interventions. Treatments considered alternative in one location may be considered conventional in another.[94] Thus, chiropractic is not considered alternative in Denmark and likewise osteopathic medicine is no longer thought of as an alternative therapy in the United States.[94]

One common feature of all definitions of alternative medicine is its designation as "other than" conventional medicine. For example, the widely referenced descriptive definition of complementary and alternative medicine devised by the US National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health (NIH), states that it is "a group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine."[1] For conventional medical practitioners, it does not necessarily follow that either it or its practitioners would no longer be considered alternative.[n 13]

Some definitions seek to specify alternative medicine in terms of its social and political marginality to mainstream healthcare.[99] This can refer to the lack of support that alternative therapies receive from the medical establishment and related bodies regarding access to research funding, sympathetic coverage in the medical press, or inclusion in the standard medical curriculum.[99] In 1993, the British Medical Association (BMA), one among many professional organizations who have attempted to define alternative medicine, stated that it[n 14] referred to "...those forms of treatment which are not widely used by the conventional healthcare professions, and the skills of which are not taught as part of the undergraduate curriculum of conventional medical and paramedical healthcare courses."[74] In a US context, an influential definition coined in 1993 by the Harvard-based physician,[100] David M. Eisenberg,[101] characterized alternative medicine "as interventions neither taught widely in medical schools nor generally available in US hospitals".[102] These descriptive definitions are inadequate in the present-day when some conventional doctors offer alternative medical treatments and CAM introductory courses or modules can be offered as part of standard undergraduate medical training;[103] alternative medicine is taught in more than 50 per cent of US medical schools and increasingly US health insurers are willing to provide reimbursement for CAM therapies. In 1999, 7.7% of US hospitals reported using some form of CAM therapy; this proportion had risen to 37.7% by 2008.[105]

An expert panel at a conference hosted in 1995 by the US Office for Alternative Medicine (OAM),[106][n 15] devised a theoretical definition[106] of alternative medicine as "a broad domain of healing resources... other than those intrinsic to the politically dominant health system of a particular society or culture in a given historical period."[107] This definition has been widely adopted by CAM researchers,[106] cited by official government bodies such as the UK Department of Health,[108] attributed as the definition used by the Cochrane Collaboration,[109] and, with some modification,[dubious discuss] was preferred in the 2005 consensus report of the US Institute of Medicine, Complementary and Alternative Medicine in the United States.[n 4]

The 1995 OAM conference definition, an expansion of Eisenberg's 1993 formulation, is silent regarding questions of the medical effectiveness of alternative therapies.[110] Its proponents hold that it thus avoids relativism about differing forms of medical knowledge and, while it is an essentially political definition, this should not imply that the dominance of mainstream biomedicine is solely due to political forces.[110] According to this definition, alternative and mainstream medicine can only be differentiated with reference to what is "intrinsic to the politically dominant health system of a particular society of culture".[111] However, there is neither a reliable method to distinguish between cultures and subcultures, nor to attribute them as dominant or subordinate, nor any accepted criteria to determine the dominance of a cultural entity.[111] If the culture of a politically dominant healthcare system is held to be equivalent to the perspectives of those charged with the medical management of leading healthcare institutions and programs, the definition fails to recognize the potential for division either within such an elite or between a healthcare elite and the wider population.[111]

Normative definitions distinguish alternative medicine from the biomedical mainstream in its provision of therapies that are unproven, unvalidated, or ineffective and support of theories with no recognized scientific basis. These definitions characterize practices as constituting alternative medicine when, used independently or in place of evidence-based medicine, they are put forward as having the healing effects of medicine, but are not based on evidence gathered with the scientific method.[1][13][24][79][80][113] Exemplifying this perspective, a 1998 editorial co-authored by Marcia Angell, a former editor of the New England Journal of Medicine, argued that:

This line of division has been subject to criticism, however, as not all forms of standard medical practice have adequately demonstrated evidence of benefit, [n 1][84] and it is also unlikely in most instances that conventional therapies, if proven to be ineffective, would ever be classified as CAM.[106]

Public information websites maintained by the governments of the US and of the UK make a distinction between "alternative medicine" and "complementary medicine", but mention that these two overlap. The National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health (NIH) (a part of the US Department of Health and Human Services) states that "alternative medicine" refers to using a non-mainstream approach in place of conventional medicine and that "complementary medicine" generally refers to using a non-mainstream approach together with conventional medicine, and comments that the boundaries between complementary and conventional medicine overlap and change with time.[1]

The National Health Service (NHS) website NHS Choices (owned by the UK Department of Health), adopting the terminology of NCCIH, states that when a treatment is used alongside conventional treatments, to help a patient cope with a health condition, and not as an alternative to conventional treatment, this use of treatments can be called "complementary medicine"; but when a treatment is used instead of conventional medicine, with the intention of treating or curing a health condition, the use can be called "alternative medicine".[115]

Similarly, the public information website maintained by the National Health and Medical Research Council (NHMRC) of the Commonwealth of Australia uses the acronym "CAM" for a wide range of health care practices, therapies, procedures and devices not within the domain of conventional medicine. In the Australian context this is stated to include acupuncture; aromatherapy; chiropractic; homeopathy; massage; meditation and relaxation therapies; naturopathy; osteopathy; reflexology, traditional Chinese medicine; and the use of vitamin supplements.[116]

The Danish National Board of Health's "Council for Alternative Medicine" (Sundhedsstyrelsens Rd for Alternativ Behandling (SRAB)), an independent institution under the National Board of Health (Danish: Sundhedsstyrelsen), uses the term "alternative medicine" for:

In General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine, published in 2000 by the World Health Organization (WHO), complementary and alternative medicine were defined as a broad set of health care practices that are not part of that country's own tradition and are not integrated into the dominant health care system.[118] Some herbal therapies are mainstream in Europe but are alternative in the US.[120]

The history of alternative medicine may refer to the history of a group of diverse medical practices that were collectively promoted as "alternative medicine" beginning in the 1970s, to the collection of individual histories of members of that group, or to the history of western medical practices that were labeled "irregular practices" by the western medical establishment.[5][121][122][123][124] It includes the histories of complementary medicine and of integrative medicine. Before the 1970s, western practitioners that were not part of the increasingly science-based medical establishment were referred to "irregular practitioners", and were dismissed by the medical establishment as unscientific and as practicing quackery.[121][122] Until the 1970's, irregular practice became increasingly marginalized as quackery and fraud, as western medicine increasingly incorporated scientific methods and discoveries, and had a corresponding increase in success of its treatments.[123] In the 1970s, irregular practices were grouped with traditional practices of nonwestern cultures and with other unproven or disproven practices that were not part of biomedicine, with the entire group collectively marketed and promoted under the single expression "alternative medicine".[5][121][122][123][125]

Use of alternative medicine in the west began to rise following the counterculture movement of the 1960s, as part of the rising new age movement of the 1970s.[5][126][127] This was due to misleading mass marketing of "alternative medicine" being an effective "alternative" to biomedicine, changing social attitudes about not using chemicals and challenging the establishment and authority of any kind, sensitivity to giving equal measure to beliefs and practices of other cultures (cultural relativism), and growing frustration and desperation by patients about limitations and side effects of science-based medicine.[5][122][123][124][125][127][128] At the same time, in 1975, the American Medical Association, which played the central role in fighting quackery in the United States, abolished its quackery committee and closed down its Department of Investigation.[121]:xxi[128] By the early to mid 1970s the expression "alternative medicine" came into widespread use, and the expression became mass marketed as a collection of "natural" and effective treatment "alternatives" to science-based biomedicine.[5][128][129][130] By 1983, mass marketing of "alternative medicine" was so pervasive that the British Medical Journal (BMJ) pointed to "an apparently endless stream of books, articles, and radio and television programmes urge on the public the virtues of (alternative medicine) treatments ranging from meditation to drilling a hole in the skull to let in more oxygen".[128] In this 1983 article, the BMJ wrote, "one of the few growth industries in contemporary Britain is alternative medicine", noting that by 1983, "33% of patients with rheumatoid arthritis and 39% of those with backache admitted to having consulted an alternative practitioner".[128]

By about 1990, the American alternative medicine industry had grown to a $27 Billion per year, with polls showing 30% of Americans were using it.[127][131] Moreover, polls showed that Americans made more visits for alternative therapies than the total number of visits to primary care doctors, and American out-of-pocket spending (non-insurance spending) on alternative medicine was about equal to spending on biomedical doctors.[121]:172 In 1991, Time magazine ran a cover story, "The New Age of Alternative Medicine: Why New Age Medicine Is Catching On".[127][131] In 1993, the New England Journal of Medicine reported one in three Americans as using alternative medicine.[127] In 1993, the Public Broadcasting System ran a Bill Moyers special, Healing and the Mind, with Moyers commenting that "...people by the tens of millions are using alternative medicine. If established medicine does not understand that, they are going to lose their clients."[127]

Another explosive growth began in the 1990s, when senior level political figures began promoting alternative medicine, investing large sums of government medical research funds into testing alternative medicine, including testing of scientifically implausible treatments, and relaxing government regulation of alternative medicine products as compared to biomedical products.[5][121]:xxi[122][123][124][125][132][133] Beginning with a 1991 appropriation of $2 million for funding research of alternative medicine research, federal spending grew to a cumulative total of about $2.5 billion by 2009, with 50% of Americans using alternative medicine by 2013.[10][134]

In 1991, pointing to a need for testing because of the widespread use of alternative medicine without authoritative information on its efficacy, United States Senator Tom Harkin used $2 million of his discretionary funds to create the Office for the Study of Unconventional Medical Practices (OSUMP), later renamed to be the Office of Alternative Medicine (OAM).[121]:170[135][136] The OAM was created to be within the National Institute of Health (NIH), the scientifically prestigious primary agency of the United States government responsible for biomedical and health-related research.[121]:170[135][136] The mandate was to investigate, evaluate, and validate effective alternative medicine treatments, and alert the public as the results of testing its efficacy.[131][135][136][137]

Sen. Harkin had become convinced his allergies were cured by taking bee pollen pills, and was urged to make the spending by two of his influential constituents.[131][135][136] Bedell, a longtime friend of Sen. Harkin, was a former member of the United States House of Representatives who believed that alternative medicine had twice cured him of diseases after mainstream medicine had failed, claiming that cow's milk colostrum cured his Lyme disease, and an herbal derivative from camphor had prevented post surgical recurrence of his prostate cancer.[121][131] Wiewel was a promoter of unproven cancer treatments involving a mixture of blood sera that the Food and Drug Administration had banned from being imported.[131] Both Bedell and Wiewel became members of the advisory panel for the OAM. The company that sold the bee pollen was later fined by the Federal Trade Commission for making false health claims about their bee-pollen products reversing the aging process, curing allergies, and helping with weight loss.[138]

In 1993, Britain's Prince Charles, who claimed that homeopathy and other alternative medicine was an effective alternative to biomedicine, established the Foundation for Integrated Health (FIH), as a charity to explore "how safe, proven complementary therapies can work in conjunction with mainstream medicine".[139] The FIH received government funding through grants from Britain's Department of Health.[139]

In 1994, Sen. Harkin (D) and Senator Orrin Hatch (R) introduced the Dietary Supplement Health and Education Act (DSHEA).[140][141] The act reduced authority of the FDA to monitor products sold as "natural" treatments.[140] Labeling standards were reduced to allow health claims for supplements based only on unconfirmed preliminary studies that were not subjected to scientific peer review, and the act made it more difficult for the FDA to promptly seize products or demand proof of safety where there was evidence of a product being dangerous.[141] The Act became known as the "The 1993 Snake Oil Protection Act" following a New York Times editorial under that name.[140]

Senator Harkin complained about the "unbendable rules of randomized clinical trials", citing his use of bee pollen to treat his allergies, which he claimed to be effective even though it was biologically implausible and efficacy was not established using scientific methods.[135][142] Sen. Harkin asserted that claims for alternative medicine efficacy be allowed not only without conventional scientific testing, even when they are biologically implausible, "It is not necessary for the scientific community to understand the process before the American public can benefit from these therapies."[140] Following passage of the act, sales rose from about $4 billion in 1994, to $20 billion by the end of 2000, at the same time as evidence of their lack of efficacy or harmful effects grew.[140] Senator Harkin came into open public conflict with the first OAM Director Joseph M. Jacobs and OAM board members from the scientific and biomedical community.[136] Jacobs' insistence on rigorous scientific methodology caused friction with Senator Harkin.[135][142][143] Increasing political resistance to the use of scientific methodology was publicly criticized by Dr. Jacobs and another OAM board member complained that "nonsense has trickled down to every aspect of this office".[135][142] In 1994, Senator Harkin appeared on television with cancer patients who blamed Dr. Jacobs for blocking their access to untested cancer treatment, leading Jacobs to resign in frustration.[135][142]

In 1995, Wayne Jonas, a promoter of homeopathy and political ally of Senator Harkin, became the director of the OAM, and continued in that role until 1999.[144] In 1997, the NCCAM budget was increased from $12 million to $20 million annually.[145] From 1990 to 1997, use of alternative medicine in the US increased by 25%, with a corresponding 50% increase in expenditures.[146] The OAM drew increasing criticism from eminent members of the scientific community with letters to the Senate Appropriations Committee when discussion of renewal of funding OAM came up.[121]:175 Nobel laureate Paul Berg wrote that prestigious NIH should not be degraded to act as a cover for quackery, calling the OAM "an embarrassment to serious scientists."[121]:175[145] The president of the American Physical Society wrote complaining that the government was spending money on testing products and practices that "violate basic laws of physics and more clearly resemble witchcraft".[121]:175[145] In 1998, the President of the North Carolina Medical Association publicly called for shutting down the OAM.[147]

In 1998, NIH director and Nobel laureate Harold Varmus came into conflict with Senator Harkin by pushing to have more NIH control of alternative medicine research.[148] The NIH Director placed the OAM under more strict scientific NIH control.[145][148] Senator Harkin responded by elevating OAM into an independent NIH "center", just short of being its own "institute", and renamed to be the National Center for Complementary and Alternative Medicine (NCCAM). NCCAM had a mandate to promote a more rigorous and scientific approach to the study of alternative medicine, research training and career development, outreach, and "integration". In 1999, the NCCAM budget was increased from $20 million to $50 million.[147][148] The United States Congress approved the appropriations without dissent. In 2000, the budget was increased to about $68 million, in 2001 to $90 million, in 2002 to $104 million, and in 2003, to $113 million.[147]

In 2004, modifications of the European Parliament's 2001 Directive 2001/83/EC, regulating all medicine products, were made with the expectation of influencing development of the European market for alternative medicine products.[149] Regulation of alternative medicine in Europe was loosened with "a simplified registration procedure" for traditional herbal medicinal products.[149][150] Plausible "efficacy" for traditional medicine was redefined to be based on long term popularity and testimonials ("the pharmacological effects or efficacy of the medicinal product are plausible on the basis of long-standing use and experience."), without scientific testing.[149][150] The Committee on Herbal Medicinal Products (HMPC) was created within the European Medicines Agency in London (EMEA). A special working group was established for homeopathic remedies under the Heads of Medicines Agencies.[149]

Through 2004, alternative medicine that was traditional to Germany continued to be a regular part of the health care system, including homeopathy and anthroposophic medicine.[149] The German Medicines Act mandated that science-based medical authorities consider the "particular characteristics" of complementary and alternative medicines.[149] By 2004, homeopathy had grown to be the most used alternative therapy in France, growing from 16% of the population using homeopathic medicine in 1982, to 29% by 1987, 36% percent by 1992, and 62% of French mothers using homeopathic medicines by 2004, with 94.5% of French pharmacists advising pregnant women to use homeopathic remedies.[151] As of 2004[update], 100 million people in India depended solely on traditional German homeopathic remedies for their medical care.[152] As of 2010[update], homeopathic remedies continued to be the leading alternative treatment used by European physicians.[151] By 2005, sales of homeopathic remedies and anthroposophical medicine had grown to $930 million Euros, a 60% increase from 1995.[151][153]

In 2008, London's The Times published a letter from Edzard Ernst that asked the FIH to recall two guides promoting alternative medicine, saying: "the majority of alternative therapies appear to be clinically ineffective, and many are downright dangerous." In 2010, Brittan's FIH closed after allegations of fraud and money laundering led to arrests of its officials.[139]

In 2009, after a history of 17 years of government testing and spending of nearly $2.5 billion on research had produced almost no clearly proven efficacy of alternative therapies, Senator Harkin complained, "One of the purposes of this center was to investigate and validate alternative approaches. Quite frankly, I must say publicly that it has fallen short. It think quite frankly that in this center and in the office previously before it, most of its focus has been on disproving things rather than seeking out and approving."[148][154][155] Members of the scientific community criticized this comment as showing Senator Harkin did not understand the basics of scientific inquiry, which tests hypotheses, but never intentionally attempts to "validate approaches".[148] Members of the scientific and biomedical communities complained that after a history of 17 years of being tested, at a cost of over $2.5 Billion on testing scientifically and biologically implausible practices, almost no alternative therapy showed clear efficacy.[10] In 2009, the NCCAM's budget was increased to about $122 million.[148] Overall NIH funding for CAM research increased to $300 Million by 2009.[148] By 2009, Americans were spending $34 Billion annually on CAM.[156]

Since 2009, according to Art. 118a of the Swiss Federal Constitution, the Swiss Confederation and the Cantons of Switzerland shall within the scope of their powers ensure that consideration is given to complementary medicine.[157]

In 2012, the Journal of the American Medical Association (JAMA) published a criticism that study after study had been funded by NCCAM, but "failed to prove that complementary or alternative therapies are anything more than placebos".[158] The JAMA criticism pointed to large wasting of research money on testing scientifically implausible treatments, citing "NCCAM officials spending $374,000 to find that inhaling lemon and lavender scents does not promote wound healing; $750,000 to find that prayer does not cure AIDS or hasten recovery from breast-reconstruction surgery; $390,000 to find that ancient Indian remedies do not control type 2 diabetes; $700,000 to find that magnets do not treat arthritis, carpal tunnel syndrome, or migraine headaches; and $406,000 to find that coffee enemas do not cure pancreatic cancer."[158] It was pointed out that negative results from testing were generally ignored by the public, that people continue to "believe what they want to believe, arguing that it does not matter what the data show: They know what works for them".[158] Continued increasing use of CAM products was also blamed on the lack of FDA ability to regulate alternative products, where negative studies do not result in FDA warnings or FDA-mandated changes on labeling, whereby few consumers are aware that many claims of many supplements were found not to have not to be supported.[158]

By 2013, 50% of Americans were using CAM.[134] As of 2013[update], CAM medicinal products in Europe continued to be exempted from documented efficacy standards required of other medicinal products.[159]

In 2014 the NCCAM was renamed to the National Center for Complementary and Integrative Health (NCCIH) with a new charter requiring that 12 of the 18 council members shall be selected with a preference to selecting leading representatives of complementary and alternative medicine, 9 of the members must be licensed practitioners of alternative medicine, 6 members must be general public leaders in the fields of public policy, law, health policy, economics, and management, and 3 members must represent the interests of individual consumers of complementary and alternative medicine.[160]

Much of what is now categorized as alternative medicine was developed as independent, complete medical systems. These were developed long before biomedicine and use of scientific methods. Each system was developed in relatively isolated regions of the world where there was little or no medical contact with pre-scientific western medicine, or with each other's systems. Examples are traditional Chinese medicine and the Ayurvedic medicine of India.

Other alternative medicine practices, such as homeopathy, were developed in western Europe and in opposition to western medicine, at a time when western medicine was based on unscientific theories that were dogmatically imposed by western religious authorities. Homeopathy was developed prior to discovery of the basic principles of chemistry, which proved homeopathic remedies contained nothing but water. But homeopathy, with its remedies made of water, was harmless compared to the unscientific and dangerous orthodox western medicine practiced at that time, which included use of toxins and draining of blood, often resulting in permanent disfigurement or death.[122]

Other alternative practices such as chiropractic and osteopathic manipulative medicine were developed in the United States at a time that western medicine was beginning to incorporate scientific methods and theories, but the biomedical model was not yet totally dominant. Practices such as chiropractic and osteopathic, each considered to be irregular practices by the western medical establishment, also opposed each other, both rhetorically and politically with licensing legislation. Osteopathic practitioners added the courses and training of biomedicine to their licensing, and licensed Doctor of Osteopathic Medicine holders began diminishing use of the unscientific origins of the field. Without the original nonscientific practices and theories, osteopathic medicine is now considered the same as biomedicine.

Further information: Rise of modern medicine

Until the 1970s, western practitioners that were not part of the medical establishment were referred to "irregular practitioners", and were dismissed by the medical establishment as unscientific, as practicing quackery.[122] Irregular practice became increasingly marginalized as quackery and fraud, as western medicine increasingly incorporated scientific methods and discoveries, and had a corresponding increase in success of its treatments.

Dating from the 1970s, medical professionals, sociologists, anthropologists and other commentators noted the increasing visibility of a wide variety of health practices that had neither derived directly from nor been verified by biomedical science.[161] Since that time, those who have analyzed this trend have deliberated over the most apt language with which to describe this emergent health field.[161] A variety of terms have been used, including heterodox, irregular, fringe and alternative medicine while others, particularly medical commentators, have been satisfied to label them as instances of quackery.[161] The most persistent term has been alternative medicine but its use is problematic as it assumes a value-laden dichotomy between a medical fringe, implicitly of borderline acceptability at best, and a privileged medical orthodoxy, associated with validated medico-scientific norms.[162] The use of the category of alternative medicine has also been criticized as it cannot be studied as an independent entity but must be understood in terms of a regionally and temporally specific medical orthodoxy.[163] Its use can also be misleading as it may erroneously imply that a real medical alternative exists.[164] As with near-synonymous expressions, such as unorthodox, complementary, marginal, or quackery, these linguistic devices have served, in the context of processes of professionalisation and market competition, to establish the authority of official medicine and police the boundary between it and its unconventional rivals.[162]

An early instance of the influence of this modern, or western, scientific medicine outside Europe and North America is Peking Union Medical College.[165][n 16][n 17]

From a historical perspective, the emergence of alternative medicine, if not the term itself, is typically dated to the 19th century.[166] This is despite the fact that there are variants of Western non-conventional medicine that arose in the late-eighteenth century or earlier and some non-Western medical traditions, currently considered alternative in the West and elsewhere, which boast extended historical pedigrees.[162] Alternative medical systems, however, can only be said to exist when there is an identifiable, regularized and authoritative standard medical practice, such as arose in the West during the nineteenth century, to which they can function as an alternative.

During the late eighteenth and nineteenth centuries regular and irregular medical practitioners became more clearly differentiated throughout much of Europe and,[168] as the nineteenth century progressed, most Western states converged in the creation of legally delimited and semi-protected medical markets.[169] It is at this point that an "official" medicine, created in cooperation with the state and employing a scientific rhetoric of legitimacy, emerges as a recognizable entity and that the concept of alternative medicine as a historical category becomes tenable.[170]

As part of this process, professional adherents of mainstream medicine in countries such as Germany, France, and Britain increasingly invoked the scientific basis of their discipline as a means of engendering internal professional unity and of external differentiation in the face of sustained market competition from homeopaths, naturopaths, mesmerists and other nonconventional medical practitioners, finally achieving a degree of imperfect dominance through alliance with the state and the passage of regulatory legislation.[162][164] In the US the Johns Hopkins University School of Medicine, based in Baltimore, Maryland, opened in 1893, with William H. Welch and William Osler among the founding physicians, and was the first medical school devoted to teaching "German scientific medicine".[171]

Buttressed by increased authority arising from significant advances in the medical sciences of the late 19th century onwardsincluding development and application of the germ theory of disease by the chemist Louis Pasteur and the surgeon Joseph Lister, of microbiology co-founded by Robert Koch (in 1885 appointed professor of hygiene at the University of Berlin), and of the use of X-rays (Rntgen rays)the 1910 Flexner Report called upon American medical schools to follow the model of the Johns Hopkins School of Medicine, and adhere to mainstream science in their teaching and research. This was in a belief, mentioned in the Report's introduction, that the preliminary and professional training then prevailing in medical schools should be reformed, in view of the new means for diagnosing and combating disease made available the sciences on which medicine depended.[n 18][173]

Putative medical practices at the time that later became known as "alternative medicine" included homeopathy (founded in Germany in the early 19c.) and chiropractic (founded in North America in the late 19c.). These conflicted in principle with the developments in medical science upon which the Flexner reforms were based, and they have not become compatible with further advances of medical science such as listed in Timeline of medicine and medical technology, 19001999 and 2000present, nor have Ayurveda, acupuncture or other kinds of alternative medicine.[citation needed]

At the same time "Tropical medicine" was being developed as a specialist branch of western medicine in research establishments such as Liverpool School of Tropical Medicine founded in 1898 by Alfred Lewis Jones, London School of Hygiene & Tropical Medicine, founded in 1899 by Patrick Manson and Tulane University School of Public Health and Tropical Medicine, instituted in 1912. A distinction was being made between western scientific medicine and indigenous systems. An example is given by an official report about indigenous systems of medicine in India, including Ayurveda, submitted by Mohammad Usman of Madras and others in 1923. This stated that the first question the Committee considered was "to decide whether the indigenous systems of medicine were scientific or not".[174][175]

By the later twentieth century the term 'alternative medicine' entered public discourse,[n 19][178] but it was not always being used with the same meaning by all parties. Arnold S. Relman remarked in 1998 that in the best kind of medical practice, all proposed treatments must be tested objectively, and that in the end there will only be treatments that pass and those that do not, those that are proven worthwhile and those that are not. He asked 'Can there be any reasonable "alternative"?'[179] But also in 1998 the then Surgeon General of the United States, David Satcher,[180] issued public information about eight common alternative treatments (including acupuncture, holistic and massage), together with information about common diseases and conditions, on nutrition, diet, and lifestyle changes, and about helping consumers to decipher fraud and quackery, and to find healthcare centers and doctors who practiced alternative medicine.[181]

By 1990, approximately 60 million Americans had used one or more complementary or alternative therapies to address health issues, according to a nationwide survey in the US published in 1993 by David Eisenberg.[182] A study published in the November 11, 1998 issue of the Journal of the American Medical Association reported that 42% of Americans had used complementary and alternative therapies, up from 34% in 1990.[146] However, despite the growth in patient demand for complementary medicine, most of the early alternative/complementary medical centers failed.[183]

Mainly as a result of reforms following the Flexner Report of 1910[184]medical education in established medical schools in the US has generally not included alternative medicine as a teaching topic.[n 20] Typically, their teaching is based on current practice and scientific knowledge about: anatomy, physiology, histology, embryology, neuroanatomy, pathology, pharmacology, microbiology and immunology.[186] Medical schools' teaching includes such topics as doctor-patient communication, ethics, the art of medicine,[187] and engaging in complex clinical reasoning (medical decision-making).[188] Writing in 2002, Snyderman and Weil remarked that by the early twentieth century the Flexner model had helped to create the 20th-century academic health center, in which education, research, and practice were inseparable. While this had much improved medical practice by defining with increasing certainty the pathophysiological basis of disease, a single-minded focus on the pathophysiological had diverted much of mainstream American medicine from clinical conditions that were not well understood in mechanistic terms, and were not effectively treated by conventional therapies.[189]

By 2001 some form of CAM training was being offered by at least 75 out of 125 medical schools in the US.[190] Exceptionally, the School of Medicine of the University of Maryland, Baltimore includes a research institute for integrative medicine (a member entity of the Cochrane Collaboration).[191][192] Medical schools are responsible for conferring medical degrees, but a physician typically may not legally practice medicine until licensed by the local government authority. Licensed physicians in the US who have attended one of the established medical schools there have usually graduated Doctor of Medicine (MD).[193] All states require that applicants for MD licensure be graduates of an approved medical school and complete the United States Medical Licensing Exam (USMLE).[193]

The British Medical Association, in its publication Complementary Medicine, New Approach to Good Practice (1993), gave as a working definition of non-conventional therapies (including acupuncture, chiropractic and homeopathy): "...those forms of treatment which are not widely used by the orthodox health-care professions, and the skills of which are not part of the undergraduate curriculum of orthodox medical and paramedical health-care courses." By 2000 some medical schools in the UK were offering CAM familiarisation courses to undergraduate medical students while some were also offering modules specifically on CAM.[195]

The Cochrane Collaboration Complementary Medicine Field explains its "Scope and Topics" by giving a broad and general definition for complementary medicine as including practices and ideas outside the domain of conventional medicine in several countriesand defined by its users as preventing or treating illness, or promoting health and well being, and which complement mainstream medicine in three ways: by contributing to a common whole, by satisfying a demand not met by conventional practices, and by diversifying the conceptual framework of medicine.[196]

Proponents of an evidence-base for medicine[n 21][198][199][200][201] such as the Cochrane Collaboration (founded in 1993 and from 2011 providing input for WHO resolutions) take a position that all systematic reviews of treatments, whether "mainstream" or "alternative", ought to be held to the current standards of scientific method.[192] In a study titled Development and classification of an operational definition of complementary and alternative medicine for the Cochrane Collaboration (2011) it was proposed that indicators that a therapy is accepted include government licensing of practitioners, coverage by health insurance, statements of approval by government agencies, and recommendation as part of a practice guideline; and that if something is currently a standard, accepted therapy, then it is not likely to be widely considered as CAM.[106]

That alternative medicine has been on the rise "in countries where Western science and scientific method generally are accepted as the major foundations for healthcare, and 'evidence-based' practice is the dominant paradigm" was described as an "enigma" in the Medical Journal of Australia.[202]

Critics in the US say the expression is deceptive because it implies there is an effective alternative to science-based medicine, and that complementary is deceptive because it implies that the treatment increases the effectiveness of (complements) science-based medicine, while alternative medicines that have been tested nearly always have no measurable positive effect compared to a placebo.[5][203][204][205]

Some opponents, focused upon health fraud, misinformation, and quackery as public health problems in the US, are highly critical of alternative medicine, notably Wallace Sampson and Paul Kurtz founders of Scientific Review of Alternative Medicine and Stephen Barrett, co-founder of The National Council Against Health Fraud and webmaster of Quackwatch.[206] Grounds for opposing alternative medicine stated in the US and elsewhere include that:

Paul Offit proposed that "alternative medicine becomes quackery" in four ways, by:[85]

A United States government agency, the National Center on Complementary and Integrative Health (NCCIH), created its own classification system for branches of complementary and alternative medicine that divides them into five major groups. These groups have some overlap, and distinguish two types of energy medicine: veritable which involves scientifically observable energy (including magnet therapy, colorpuncture and light therapy) and putative, which invokes physically undetectable or unverifiable energy.[215]

Alternative medicine practices and beliefs are diverse in their foundations and methodologies. The wide range of treatments and practices referred to as alternative medicine includes some stemming from nineteenth century North America, such as chiropractic and naturopathy, others, mentioned by Jtte, that originated in eighteenth- and nineteenth-century Germany, such as homeopathy and hydropathy,[164] and some that have originated in China or India, while African, Caribbean, Pacific Island, Native American, and other regional cultures have traditional medical systems as diverse as their diversity of cultures.[1]

Examples of CAM as a broader term for unorthodox treatment and diagnosis of illnesses, disease, infections, etc.,[216] include yoga, acupuncture, aromatherapy, chiropractic, herbalism, homeopathy, hypnotherapy, massage, osteopathy, reflexology, relaxation therapies, spiritual healing and tai chi.[216] CAM differs from conventional medicine. It is normally private medicine and not covered by health insurance.[216] It is paid out of pocket by the patient and is an expensive treatment.[216] CAM tends to be a treatment for upper class or more educated people.[146]

The NCCIH classification system is -

Alternative therapies based on electricity or magnetism use verifiable electromagnetic fields, such as pulsed fields, alternating-current, or direct-current fields in an unconventional manner rather than claiming the existence of imponderable or supernatural energies.[1]

Substance based practices use substances found in nature such as herbs, foods, non-vitamin supplements and megavitamins, and minerals, and includes traditional herbal remedies with herbs specific to regions where the cultural practices.[1] Nonvitamin supplements include fish oil, Omega-3 fatty acid, glucosamine, echinacea, flaxseed oil or pills, and ginseng, when used under a claim to have healing effects.[66]

Mind-body interventions, working under the premise that the mind can affect "bodily functions and symptoms",[1] include healing claims made in hypnotherapy,[217] and in guided imagery, meditation, progressive relaxation, qi gong, tai chi and yoga.[1] Meditation practices including mantra meditation, mindfulness meditation, yoga, tai chi, and qi gong have many uncertainties. According to an AHRQ review, the available evidence on meditation practices through September 2005 is of poor methodological quality and definite conclusions on the effects of meditation in healthcare cannot be made using existing research.[218][219]

Naturopathy is based on a belief in vitalism, which posits that a special energy called vital energy or vital force guides bodily processes such as metabolism, reproduction, growth, and adaptation.[41] The term was coined in 1895[220] by John Scheel and popularized by Benedict Lust, the "father of U.S. naturopathy".[221] Today, naturopathy is primarily practiced in the United States and Canada.[222] Naturopaths in unregulated jurisdictions may use the Naturopathic Doctor designation or other titles regardless of level of education.[223]

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Posted: October 20, 2016 at 1:44 am

Dr. Behlen studied at the University of Wisconsin-Oshkosh and the University of Cambridge for her undergraduate studies of Biological Sciences. She graduated with her medical training from Texas Health & Science University. During the course of her Medical training she specialized in Pain Management and Sport's Medicine. At Concordia University Dr. Behlen treated athletes and completed her Sport's Medicine training. Her boards were completed in San Antonio, Texas - Medical Branch. While in San Antonio she spent time treating athletes in the NBA. With over a decade and a half of working in the healthcare field, Dr. Behlen found a calling in Integrative Pain Management. She also has a large fertility patient population. Dr. Behlen is a Fellow with the American Association of Integrative Medicine (FAAIM). She has appeared on the nationally syndicated NBC show, Dr.OZ, as a physician commentator. She is also on the National Pain Advisory Board for Chronic Migraines. As of 2014 she is one of the newest elected Board Members of the American Association of Integrative Medicine. She is a Diplomate in the College of Physicians (DCP), Diplomate in the College of Pain Management (DCPM), Diplomate in the College of Pharmaceutical & Apothecary Sciences (DCPAS), and Diplomate in the College of Acupuncture & Neuromuscular Therapy (DCANT). She holds the highest National board certification for Acupuncture & Oriental Medicine (NCCAOM). Dr. Behlen is a member of American Association of Physicians & Surgeons, American Association of Integrative Medicine, American Chronic Pain Association and American Pregnancy Association. Currently Dr. Behlen is the only Doctor in the state of Oklahoma who has achieved these board certifications. She is also ranked as the #1 Provider for Acupuncture in the state.

Orthomolecular medicine, as conceptualized by double-Nobel laureate Linus Pauling, aims to restore the optimum environment of the body by correcting imbalances or deficiencies based on individual biochemistry, using substances natural to the body such as vitamins, minerals, amino acids, trace elements and fatty acids. The key concept in orthomolecular medicine is that genetic factors affect not only the physical characteristics of individuals, but also their biochemical makeup. Biochemical pathways of the body have significant genetic variability and diseases such as atherosclerosis, cancer, schizophrenia or depression are associated with specific biochemical abnormalities which are causal or contributing factors of the illness.

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