StemCell Therapy

Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not, in essence, doing their job. Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic defects that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases, like cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancers, arthritis, and infectious diseases. Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, like intelligence or appearance.

Gene therapy has grown out of the science of genetics or how heredity works. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within the cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of a single molecule of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that determine inherited characteristics.

A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each other. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen molecules and arranged in specific sequences. Millions of these base pairs, or sequences, can make up a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs ultimately direct an organism's growth and characteristics through the production of certain chemicals, primarily proteins, which carry out most of the body's chemical functions and biological reactions.

Scientists have long known that alterations in genes present within cells can cause inherited diseases like cystic fibrosis, sickle-cell anemia, and hemophilia. Similarly, errors in the total number of chromosomes can cause conditions such as Down syndrome or Turner's syndrome. As the study of genetics advanced, however, scientists learned that an altered genetic sequence also can make people more susceptible to diseases, like atherosclerosis, cancer, and even schizophrenia. These diseases have a genetic component, but also are influenced by environmental factors (like diet and lifestyle). The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process by either replacing missing genes or providing copies of functioning genes to replace nonfunctioning ones. The inserted genes can be naturally-occurring genes that produce the desired effect or may be genetically engineered (or altered) genes.

Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing the specific genetic sequence desired, then inserting it into the DNA of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.

There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations. Most of the current work in applying gene therapy, however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual patient.

In both types of therapy, scientists need something to transport either the entire gene or a recombinant DNA to the cell's nucleus, where the chromosomes and DNA reside. In essence, vectors are molecular delivery trucks. One of the first and most popular vectors developed were viruses because they invade cells as part of the natural infection process. Viruses have the potential to be excellent vectors because they have a specific relationship with the host in that they colonize certain cell types and tissues in specific organs. As a result, vectors are chosen according to their attraction to certain cells and areas of the body.

One of the first vectors used was retroviruses. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biological action. They also have learned how to remove the genetic information that governs viral replication, thus reducing the chances of infection.

Retroviruses work best in actively dividing cells, but cells in the body are relatively stable and do not divide often. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from the patient's body, and the virus, or vector, carrying the gene is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they will provide the desired therapy.

Another class of viruses, called the adenoviruses, also may prove to be good gene vectors. These viruses can effectively infect nondividing cells in the body, where the desired gene product then is expressed naturally. In addition to being a more efficient approach to gene transportation, these viruses, which cause respiratory infections, are more easily purified and made stable than retroviruses, resulting in less chance of an unwanted viral infection. However, these viruses live for several days in the body, and some concern surrounds the possibility of infecting others with the viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a herpes virus that infects nerve cells.

Scientists also have delved into nonviral vectors. These vectors rely on the natural biological process in which cells uptake (or gather) macromolecules. One approach is to use liposomes, globules of fat produced by the body and taken up by cells. Scientists also are investigating the introduction of raw recombinant DNA by injecting it into the bloodstream or placing it on microscopic beads of gold shot into the skin with a "gene-gun." Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that have a high molecular weight and formed by smaller molecules of the same or similar substances), is "constructed" in the laboratory by combining these smaller molecules. They have been used in manufacturing Styrofoam, polyethylene cartons, and Plexiglass. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They also can be designed to form an affinity for particular cell membranes by attaching to certain sugars and protein groups.

In the early 1970s, scientists proposed "gene surgery" for treating inherited diseases caused by faulty genes. The idea was to take out the disease-causing gene and surgically implant a gene that functioned properly. Although sound in theory, scientists, then and now, lack the biological knowledge or technical expertise needed to perform such a precise surgery in the human body.

However, in 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific type of protein) for correcting the disease was injected into a group of cells for replication. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease, thus correcting the genetic defect that caused the disease.

As the science of genetics advanced throughout the 1980s, gene therapy gained an established foothold in the minds of medical scientists as a promising approach to treatments for specific diseases. One of the major reasons for the growth of gene therapy was scientists' increasing ability to identify the specific genetic malfunctions that caused inherited diseases. Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific genetic abnormalities in one or more genes occurred in successive generations of certain family members who suffered from diseases like intestinal cancer, bipolar disorder, Alzheimer's disease, heart disease, diabetes, and many more. Although the genes may not be the only cause of the disease in all cases, they may make certain individuals more susceptible to developing the disease because of environmental influences, like smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic component.

On September 14, 1990, a four-year old girl suffering from a genetic disorder that prevented her body from producing a crucial enzyme became the first person to undergo gene therapy in the United States. Because her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening infections. W. French Anderson and colleagues at the National Institutes of Health's Clinical Center in Bethesda, Maryland, took white blood cells (which are crucial to proper immune system functioning) from the girl, inserted ADA producing genes into them, and then transfused the cells back into the patient. Although the young girl continued to show an increased ability to produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.

Nevertheless, a new era of gene therapy began as more and more scientists sought to conduct clinical trial (testing in humans) research in this area. In that same year, gene therapy was tested on patients suffering from melanoma (skin cancer). The goal was to help them produce antibodies (disease fighting substances in the immune system) to battle the cancer.

These experiments have spawned an ever growing number of attempts at gene therapies designed to perform a variety of functions in the body. For example, a gene therapy for cystic fibrosis aims to supply a gene that alters cells, enabling them to produce a specific protein to battle the disease. Another approach was used for brain cancer patients, in which the inserted gene was designed to make the cancer cells more likely to respond to drug treatment. Another gene therapy approach for patients suffering from artery blockage, which can lead to strokes, induces the growth of new blood vessels near clogged arteries, thus ensuring normal blood circulation.

Currently, there are a host of new gene therapy agents in clinical trials. In the United States, both nucleic acid based (in vivo ) treatments and cell-based (ex vivo ) treatments are being investigated. Nucleic acid based gene therapy uses vectors (like viruses) to deliver modified genes to target cells. Cell-based gene therapy techniques remove cells from the patient in order to genetically alter them then reintroduce them to the patient's body. Presently, gene therapies for the following diseases are being developed: cystic fibrosis (using adenoviral vector), HIV infection (cell-based), malignant melanoma (cell-based), Duchenne muscular dystrophy (cell-based), hemophilia B (cell-based), kidney cancer (cell-based), Gaucher's Disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector). When a cell or individual is treated using gene therapy and successful incorporation of engineered genes has occurred, the cell or individual is said to be transgenic.

The medical establishment's contribution to transgenic research has been supported by increased government funding. In 1991, the U.S. government provided $58 million for gene therapy research, with increases in funding of $15-40 million dollars a year over the following four years. With fierce competition over the promise of societal benefit in addition to huge profits, large pharmaceutical corporations have moved to the forefront of transgenic research. In an effort to be first in developing new therapies, and armed with billions of dollars of research funds, such corporations are making impressive strides toward making gene therapy a viable reality in the treatment of once elusive diseases.

The potential scope of gene therapy is enormous. More than 4,200 diseases have been identified as resulting directly from abnormal genes, and countless others that may be partially influenced by a person's genetic makeup. Initial research has concentrated on developing gene therapies for diseases whose genetic origins have been established and for other diseases that can be cured or improved by substances genes produce.

The following are examples of potential gene therapies. People suffering from cystic fibrosis lack a gene needed to produce a salt-regulating protein. This protein regulates the flow of chloride into epithelial cells, (the cells that line the inner and outer skin layers) that cover the air passages of the nose and lungs. Without this regulation, patients with cystic fibrosis build up a thick mucus that makes them prone to lung infections. A gene therapy technique to correct this abnormality might employ an adenovirus to transfer a normal copy of what scientists call the cystic fibrosis transmembrane conductance regulator, or CTRF, gene. The gene is introduced into the patient by spraying it into the nose or lungs. Researchers announced in 2004 that they had, for the first time, treated a dominant neurogenerative disease called Spinocerebella ataxia type 1, with gene therapy. This could lead to treating similar diseases such as Huntingtons disease. They also announced a single intravenous injection could deliver therapy to all muscles, perhaps providing hope to people with muscular dystrophy.

Familial hypercholesterolemia (FH) also is an inherited disease, resulting in the inability to process cholesterol properly, which leads to high levels of artery-clogging fat in the blood stream. Patients with FH often suffer heart attacks and strokes because of blocked arteries. A gene therapy approach used to battle FH is much more intricate than most gene therapies because it involves partial surgical removal of patients' livers (ex vivo transgene therapy). Corrected copies of a gene that serve to reduce cholesterol build-up are inserted into the liver sections, which then are transplanted back into the patients.

Gene therapy also has been tested on patients with AIDS. AIDS is caused by the human immunodeficiency virus (HIV), which weakens the body's immune system to the point that sufferers are unable to fight off diseases like pneumonias and cancer. In one approach, genes that produce specific HIV proteins have been altered to stimulate immune system functioning without causing the negative effects that a complete HIV molecule has on the immune system. These genes are then injected in the patient's blood stream. Another approach to treating AIDS is to insert, via white blood cells, genes that have been genetically engineered to produce a receptor that would attract HIV and reduce its chances of replicating. In 2004, researchers reported that had developed a new vaccine concept for HIV, but the details were still in development.

Several cancers also have the potential to be treated with gene therapy. A therapy tested for melanoma, or skin cancer, involves introducing a gene with an anticancer protein called tumor necrosis factor (TNF) into test tube samples of the patient's own cancer cells, which are then reintroduced into the patient. In brain cancer, the approach is to insert a specific gene that increases the cancer cells' susceptibility to a common drug used in fighting the disease. In 2003, researchers reported that they had harnessed the cell killing properties of adenoviruses to treat prostate cancer. A 2004 report said that researchers had developed a new DNA vaccine that targeted the proteins expressed in cervical cancer cells.

Gaucher disease is an inherited disease caused by a mutant gene that inhibits the production of an enzyme called glucocerebrosidase. Patients with Gaucher disease have enlarged livers and spleens and eventually their bones deteriorate. Clinical gene therapy trials focus on inserting the gene for producing this enzyme.

Gene therapy also is being considered as an approach to solving a problem associated with a surgical procedure known as balloon angioplasty. In this procedure, a stent (in this case, a type of tubular scaffolding) is used to open the clogged artery. However, in response to the trauma of the stent insertion, the body initiates a natural healing process that produces too many cells in the artery and results in restenosis, or reclosing of the artery. The gene therapy approach to preventing this unwanted side effect is to cover the outside of the stents with a soluble gel. This gel contains vectors for genes that reduce this overactive healing response.

Regularly throughout the past decade, and no doubt over future years, scientists have and will come up with new possible ways for gene therapy to help treat human disease. Recent advancements include the possibility of reversing hearing loss in humans with experimental growing of new sensory cells in adult guinea pigs, and avoiding amputation in patients with severe circulatory problems in their legs with angiogenic growth factors.

Although great strides have been made in gene therapy in a relatively short time, its potential usefulness has been limited by lack of scientific data concerning the multitude of functions that genes control in the human body. For instance, it is now known that the vast majority of genetic material does not store information for the creation of proteins, but rather is involved in the control and regulation of gene expression, and is, thus, much more difficult to interpret. Even so, each individual cell in the body carries thousands of genes coding for proteins, with some estimates as high as 150,000 genes. For gene therapy to advance to its full potential, scientists must discover the biological role of each of these individual genes and where the base pairs that make them up are located on DNA.

To address this issue, the National Institutes of Health initiated the Human Genome Project in 1990. Led by James D. Watson (one of the co-discoverers of the chemical makeup of DNA) the project's 15-year goal is to map the entire human genome (a combination of the words gene and chromosomes). A genome map would clearly identify the location of all genes as well as the more than three billion base pairs that make them up. With a precise knowledge of gene locations and functions, scientists may one day be able to conquer or control diseases that have plagued humanity for centuries.

Scientists participating in the Human Genome Project identified an average of one new gene a day, but many expected this rate of discovery to increase. By the year 2005, their goal was to determine the exact location of all the genes on human DNA and the exact sequence of the base pairs that make them up. Some of the genes identified through this project include a gene that predisposes people to obesity, one associated with programmed cell death (apoptosis), a gene that guides HIV viral reproduction, and the genes of inherited disorders like Huntington's disease, Lou Gehrig's disease, and some colon and breast cancers. In April 2003, the finished sequence was announced, with 99% of the human genome's gene-containing regions mapped to an accuracy of 99.9%.

Gene therapy seems elegantly simple in its concept: supply the human body with a gene that can correct a biological malfunction that causes a disease. However, there are many obstacles and some distinct questions concerning the viability of gene therapy. For example, viral vectors must be carefully controlled lest they infect the patient with a viral disease. Some vectors, like retroviruses, also can enter cells functioning properly and interfere with the natural biological processes, possibly leading to other diseases. Other viral vectors, like the adenoviruses, often are recognized and destroyed by the immune system so their therapeutic effects are short-lived. Maintaining gene expression so it performs its role properly after vector delivery is difficult. As a result, some therapies need to be repeated often to provide long-lasting benefits.

One of the most pressing issues, however, is gene regulation. Genes work in concert to regulate their functioning. In other words, several genes may play a part in turning other genes on and off. For example, certain genes work together to stimulate cell division and growth, but if these are not regulated, the inserted genes could cause tumor formation and cancer. Another difficulty is learning how to make the gene go into action only when needed. For the best and safest therapeutic effort, a specific gene should turn on, for example, when certain levels of a protein or enzyme are low and must be replaced. But the gene also should remain dormant when not needed to ensure it doesn't oversupply a substance and disturb the body's delicate chemical makeup.

One approach to gene regulation is to attach other genes that detect certain biological activities and then react as a type of automatic off-and-on switch that regulates the activity of the other genes according to biological cues. Although still in the rudimentary stages, researchers are making headway in inhibiting some gene functioning by using a synthetic DNA to block gene transcriptions (the copying of genetic information). This approach may have implications for gene therapy.

While gene therapy holds promise as a revolutionary approach to treating disease, ethical concerns over its use and ramifications have been expressed by scientists and lay people alike. For example, since much needs to be learned about how these genes actually work and their long-term effect, is it ethical to test these therapies on humans, where they could have a disastrous result? As with most clinical trials concerning new therapies, including many drugs, the patients participating in these studies usually have not responded to more established therapies and often are so ill the novel therapy is their only hope for long-term survival.

Another questionable outgrowth of gene therapy is that scientists could possibly manipulate genes to genetically control traits in human offspring that are not health related. For example, perhaps a gene could be inserted to ensure that a child would not be bald, a seemingly harmless goal. However, what if genetic manipulation was used to alter skin color, prevent homosexuality, or ensure good looks? If a gene is found that can enhance intelligence of children who are not yet born, will everyone in society, the rich and the poor, have access to the technology or will it be so expensive only the elite can afford it?

The Human Genome Project, which plays such an integral role for the future of gene therapy, also has social repercussions. If individual genetic codes can be determined, will such information be used against people? For example, will someone more susceptible to a disease have to pay higher insurance premiums or be denied health insurance altogether? Will employers discriminate between two potential employees, one with a "healthy" genome and the other with genetic abnormalities?

Some of these concerns can be traced back to the eugenics movement popular in the first half of the twentieth century. This genetic "philosophy" was a societal movement that encouraged people with "positive" traits to reproduce while those with less desirable traits were sanctioned from having children. Eugenics was used to pass strict immigration laws in the United States, barring less suitable people from entering the country lest they reduce the quality of the country's collective gene pool. Probably the most notorious example of eugenics in action was the rise of Nazism in Germany, which resulted in the Eugenic Sterilization Law of 1933. The law required sterilization for those suffering from certain disabilities and even for some who were simply deemed "ugly." To ensure that this novel science is not abused, many governments have established organizations specifically for overseeing the development of gene therapy. In the United States, the Food and Drug Administration (FDA) and the National Institutes of Health require scientists to take a precise series of steps and meet stringent requirements before proceeding with clinical trials. As of mid-2004, more than 300 companies were carrying out gene medicine developments and 500 clinical trials were underway. How to deliver the therapy is the key to unlocking many of the researchers discoveries.

In fact, gene therapy has been immersed in more controversy and surrounded by more scrutiny in both the health and ethical arena than most other technologies (except, perhaps, for cloning) that promise to substantially change society. Despite the health and ethical questions surrounding gene therapy, the field will continue to grow and is likely to change medicine faster than any previous medical advancement.

Cell The smallest living unit of the body that groups together to form tissues and help the body perform specific functions.

Chromosome A microscopic thread-like structure found within each cell of the body, consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the total number of chromosomes or their shape and size (structure) may lead to physical or mental abnormalities.

Clinical trial The testing of a drug or some other type of therapy in a specific population of patients.

Clone A cell or organism derived through asexual (without sex) reproduction containing the identical genetic information of the parent cell or organism.

Deoxyribonucleic acid (DNA) The genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.

Embryo The earliest stage of development of a human infant, usually used to refer to the first eight weeks of pregnancy. The term fetus is used from roughly the third month of pregnancy until delivery.

Enzyme A protein that causes a biochemical reaction or change without changing its own structure or function.

Eugenics A social movement in which the population of a society, country, or the world is to be improved by controlling the passing on of hereditary information through mating.

Gene A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.

Gene transcription The process by which genetic information is copied from DNA to RNA, resulting in a specific protein formation.

Genetic engineering The manipulation of genetic material to produce specific results in an organism.

Genetics The study of hereditary traits passed on through the genes.

Germ-line gene therapy The introduction of genes into reproductive cells or embryos to correct inherited genetic defects that can cause disease.

Liposome Fat molecule made up of layers of lipids.

Macromolecules A large molecule composed of thousands of atoms.

Nitrogen A gaseous element that makes up the base pairs in DNA.

Nucleus The central part of a cell that contains most of its genetic material, including chromosomes and DNA.

Protein Important building blocks of the body, composed of amino acids, involved in the formation of body structures and controlling the basic functions of the human body.

Somatic gene therapy The introduction of genes into tissue or cells to treat a genetic related disease in an individual.

Vectors Something used to transport genetic information to a cell.

Abella, Harold. "Gene Therapy May Save Limbs." Diagnostic Imaging (May 1, 2003): 16.

Christensen R. "Cutaneous Gene TherapyAn Update." Histochemical Cell Biology (January 2001): 73-82.

"Gene Therapy Important Part of Cancer Research." Cancer Gene Therapy Week (June 30, 2003): 12.

"Initial Sequencing and Analysis of the Human Genome." Nature (February 15, 2001): 860-921.

Kingsman, Alan. "Gene Therapy Moves On." SCRIP World Pharmaceutical News (July 7, 2004): 19:ndash;21.

Nevin, Norman. "What Has Happened to Gene Therapy?" European Journal of Pediatrics (2000): S240-S242.

"New DNA Vaccine Targets Proteins Expressed in Cervical Cancer Cells." Gene Therapy Weekly (September 9, 2004): 14.

"New Research on the Progress of Gene Therapy Presented at Meeting." Obesity, Fitness & Wellness Week (July 3, 2004): 405.

Pekkanen, John. "Genetics: Medicine's Amazing Leap." Readers Digest (September 1991): 23-32.

Silverman, Jennifer, and Steve Perlstein. "Genome Project Completed." Family Practice News (May 15, 2003): 50-51.

"Study Highlights Potential Danger of Gene Therapy." Drug Week (June 20, 2003): 495.

"Study May Help Scientists Develop Safer Mthods for Gene Therapy." AIDS Weekly (June 30, 2003): 32.

Trabis, J. "With Gene Therapy, Ears Grow New Sensory Cells." Science News (June 7, 2003): 355.

National Human Genome Research Institute. The National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-2433. http://www.nhgri.nih.gov.

Online Mendelian Inheritance in Man. Online genetic testing information sponsored by National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/Omim/.

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gene therapy facts, information, pictures | Encyclopedia.com ...

By the time 2-year-old Calliope Joy Carr, of Bala Cynwyd, was diagnosed with an incurable degenerative brain disease, two children with the same deadly ailment, just 20 miles away, were being offered a tenuous lifeline.

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Eli and Ella Vivian, 7- and 4-year-old siblings from Upper Providence Township, also had metachromatic leukodystrophy, a genetic disease that robs its victims, mostly children, of their motor and mental skills and, eventually, their lives. But because their symptoms were less severe than Calliope's, the Vivian children were eligible for a gene therapy clinical trial in Milan, Italy, that she was not.

Today, at 7, Calliope is bedridden, able to smile at her family and favorite TV programs and move her head slightly, but unable to speak. MLD continues to take its toll, as well, on Eli and Ella Vivian, 11 and 8. But they attend school, play, and are rambunctious in a way that Calliope has not been since three months after her diagnosis, when she spoke for the last time, saying "Daddy."

Eli and Ella "shouldn't be able to do what they are doing," said their mother, Becky Vivian. "We have hope and we are grateful, but we are realistic. It may not save their lives, just prolong it."

One in 40,000 infants is born with MLD. Now, gene therapy - the transfer of normal genes into cells to replace missing or defective ones - is engendering hope in families that their children can be more effectively treated, if not as yet cured.

Other recent developments have further boosted that optimism.

Alessandra Biffi, the physician/researcher who led the trial at Milan's San Raffaele Hospital, now directs the gene therapy program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Further, the experimental treatment has been licensed by GlaxoSmithKline, which has major operations in Philadelphia. And the Leukodystrophy Center at Children's Hospital of Philadelphia, opened in 2015, is delivering cutting-edge care.

Andrew Shenker, vice president in GSK's rare diseases unit and project physician leader for its MLD program, cautions that the research begun in Italy in 2009 is ongoing. The pharmaceutical company expects to submit data from the trial to government regulators in 2018, after which those agencies will conduct their own reviews.

Children with MLD lack an enzyme in key cells needed for the production and maintenance of myelin, which protects nerves and facilitates the transmission of impulses within the brain. Without myelin, communication is disrupted. The patient loses basic functions, resulting in paralysis, blindness, seizures, and eventual death.

The condition is passed down from two carrier parents; any child they produce has a 1 in 4 chance of having the disease. Survival ages vary, depending on when MLD is discovered and the level of medical care. In the absence of treatment, the mean age of death for a child diagnosed at 1 to 2 years of age is 4.2 years; for those diagnosed between 4 and 14, the mean age is 17.4 years.

The most common form of treatment is stem cell therapy, but results have been "mixed" and "disappointing," Shenker said.

Other researchers are investigating treatments including enzyme replacement and gene therapy, and screening procedures to diagnose the disease at birth, said Dean Suhr, president of the Oregon-based MLD Foundation.

Results published so far on the Milan trial indicate that when treatment is administered before patients show obvious signs of the disease, the onset of symptoms is delayed, and their severity lessened.

Gene therapy appears most effective with children diagnosed before age 2 and treated before they show symptoms, Shenker said. Research on the treatment's benefit for older youngsters is ongoing.

Two children who were treated after the onset of symptoms died while participating in the trial, but their deaths were attributed to the progression of the disease, not the safety of the closely-monitored treatment, Shenker said.

Ella Vivian was one of the test cases. Because his symptoms were more advanced than hers, Eli was not part of the trial, but was treated under a "compassionate use protocol." The Inquirer published an article about the siblings in January of 2013 before the family left for Italy.

They spent six months in Milan, during which they received massive doses of chemotherapy to kill the diseased stem cells and make room for new cells containing the healthy gene to take hold. Researchers used a form of the HIV virus, minus the disease component, as a transfer agent to insert the genes.

Becky Vivian, 44, a Gymboree teacher, accompanied her children to Milan, while husband Steve stayed home with older sons Eric and Evan.

"Right now, we know they are a miracle," she said. ". . . Unfortunately, we can still see progression of the disease, albeit slowly."

Eli has difficulty standing up straight and walking, and cannot run. Ella has pain in her arms and legs, and her walking is getting slower, her writing less legible.

They have regular physical and occupational therapy, but are on no medication, their mother said. They also return to Milan every six months for checkups. In several weeks, they will be visiting Biffi in Boston for testing.

The Vivian siblings give Calliope's parents hope - if not for their daughter, then for other children with the disease and those diagnosed in the future.

Calliope, called "Cal," was diagnosed at 21/2, shortly after her parents noticed she was losing her balance on stairs.

"When we found out Cal was sick, we were really lost," said her mother, Maria Kefalas, 49, a sociology professor at Saint Joseph's University.

Three months later, Cal said her last word.

"It was like she fell off a cliff," said her father, Patrick Carr, 50, an associate professor and director of the Criminal Justice Program at Rutgers University-New Brunswick.

Cal has been in hospice care for four years, but the little girl her family knew at 2 is still there, Carr says. She loves her favorite TV shows and dolls, and smiles when brother P.J., 12, gets scolded.

Shortly after their daughter was diagnosed, Kefalas and Carr created the Calliope Joy Foundation, which has raised $300,000 - much of it by selling cupcakes - for research and patient care, including $60,000 for the Leukodystrophy Center of Excellence. The annual fund-raiser is May 6 at Lincoln Financial Field.

The charity also supports families like the Vivians, who got a donation to help with travel to Italy.

Becky Vivian says she is in a desperate race to save her children. And the family isn't letting up.

When Eli struggles with a tall chair and asks for a boost, his mother says no.

"Once we give in, it'll be time for a wheelchair. So I say, 'Eli, you've got to do it yourself.' "

kholmes@phillynews.com

610-313-8211

For information on the Calliope Joy Foundation, visit http://www.thecalliopejoyfoundation.org/

For updates on the Vivian children, visit http://www.facebook.com/Eli-Ellas-Prayer-Warriors-393482210723355/

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The promise of gene therapy for Eli and Ella, but not ...

It Can Help Your Heart continued...

Make sure you have salmon and other fish like trout and herring. Theyre high in omega-3 fatty acids, which help reduce the risk of heart disease and slightly lower blood pressure, among other benefits. Shoot for two servings a week.

You should also know thatthe fiber in veggies -- also found in whole grains -- helps lower your odds of cardiovascular disease. It also helps digestion and regularity, which often are a problem for older adults.

Remember that no one food is going to help your heart, any more than just one would help your brain or your bones or your muscles or any other part of your anatomy.

You need a complete, healthy diet.

If youre eating a lot of fish but, in addition to that, youre living on ice cream and candy and stuff like that, Rock says, its not going to save you.

A loss of memory, a big worry among some older adults, has been linked to, among other things, a lack of vitamin B12. You can get that in:

Alzheimers disease has been linked to chronic inflammation, which can be caused by foods like white bread, french fries, red meat, sugary beverages, and margarine.

The science is still emergingon the relationship between some foods and brain health. Check with your doctor or dietitian.

There was some issue with the Food and Drug Administration disallowing food claims for memory loss, says Adam Drewnowski, the director of the Nutritional Sciences Program at the University of Washington.

I would not want to identify a specific food that prevents memory loss. I probably would tell someone that if you want to be functioning well, then some fruits and antioxidants will do better for you than another slice of cake.

Antioxidants, found in many vegetables and in fruits like blueberries, help reduce inflammation. They also help you get rid of damaging stuff created when you convert food into energy.

Again, though, its important to realize that good brain function may be as much about what you dont eat as what you do.

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Eating for Longevity: Foods for a Long, Healthy Life

Physicians and surgeons help to keep people - from infants to the elderly - as healthy as possible. These individuals provide diagnoses and treatments for a wide variety of ailments, and preventative care and early detection for more serious illnesses. Whether you love or hate going to the doctor, the fact is your physician is there to listen to your health concerns, take preventative measures against diseases and advise you on your optionsfor stayingin tip-top shape.

In 2013, there were more than 1 million doctors of medicine in the U.S., over 854,000 of which were active. Additionally, in 2012, there were about 18,000 active general surgeons in the country. It's important to know which type of physician or surgeon you need, how to choose the best one, and account for other considerations in order to stay healthy.

Patients can choose from a wide variety of physicians depending on doctor specialty and what problems they are experiencing. Here are a few of the most common types of physicians that you may see in your lifetime:

General Practitioner Your GP is the doctor that you go to for regular checkups, vaccines and to identify health issues. GPs can treat many different illnesses and injuries, from the common cold to a broken arm. If your health requires a second opinion or expert care, the GP will refer you to a specialist who has the skills to focus in on the issue.

Cardiologist Heart attacks and heart disease are some of the most common afflictions seen across the country, making cardiologists important to your long-term health. These physicians specialize in studying and treating the heart and related diseases.

Dentist Other than a GP, the dentist is likely the most common physician you'll ever see. These professionals work with the human mouth, ensuring that your teeth and gum health are up to par. Patients typically go to the dentist twice a year.

Dermatologist Dermatologists are focused on skin-related issues and diseases, from skin cancers, to acute acne, eczema, psoriasis, and general cosmetic concerns like aging and scars. Most will also perform annual or semi-annual mole checks to screen for any signs of melanoma, the most serious form of skin cancer.

ENT If you have a number of sinus infections or have had your tonsils taken out, you've likely seen an ENT specialist. ENTs handle ailments related to the ear, nose and throat, often related to taking out tonsils and treating hearing issues.

OB/GYN For many women, their gynecologist and obstetrician are the same person. These professionals work with the female reproductive system to focus on reproductive health, fertility issues, prenatal care, options for new and expectant mothers, neonatal care and childbirth. OB/GYNs can also help in the early detection of breast or cervical cancer.

There are obviously a number of physicians that you can choose from, but how do you know if they'rethe best choice for you? Here are a few considerations to help you pick a physician:

Look at Your Insurance Before you get down to the details, you need to verify which doctors are covered by your insurance and whether they are in or out of your carrier's network. Rates may be cheaper if the doc is in network a doctor can be covered by your insurance but not necessarily in network. Out of network is typically more expensive.Doctors often add and drop plans, so it's important to ensure that your options are compatible with your insurance plan. Doing your homework will help you avoid unexpected expenses.

Check for Board Certification Your physician should be certified through the American Board of Medical Specialties. Doctors must earn a medical degree from a qualified school, complete three to seven years of residency training, be licensed by a state medical board and pass one or more ABMS exams to be certified.

Examine the Reviews Reviewsof a doctor can reveal a lot about what your experience may be like. People may grade on staff friendliness, availability and effectiveness of treatment. Looking at these evaluations and getting recommendations from family and friends can direct you toward a physician for your needs.

Surgeons can literally hold your life in their hands, and it's important to find the best one that can put you at ease and treat you effectively

Compatibility Factor You need to feel comfortable with your surgeon. It's important to communicate your concerns and that your surgeon can respond adequately. Surgeons should be willing to go over the details of your procedure and answer any questions that you may have. They must take the time to discuss and address your worries.

Expertise Level If you're going in for surgery, you want someone that knows what they're doing and has a high success rate. Ask how often the surgeon performs this surgery and try to find one that regularly does it. This will give you peace of mind that you're in capable hands.

Your decisionon a physician or surgeon can be majorly affected by the insurance plan you have. You may have insurance through employment, your spouse, your parents if you're under 26, or the marketplace if the previous options don't apply to you. It's important to understand how your insurance works to have the full picture of what you'll need to pay for.

Your insurance will have a deductible, which is the amount that you're responsible to pay for covered medical expenses. Some plans have coinsurances, where you must pay a certain percentage of the bill, and insurance will cover the rest. Co-pays state a flat rate for certain services, like paying $20 when you visit your GP or a $100 co-pay for an emergency room visit. Once you reach your out-of-pocket maximum, which will differ if you're an individual or within a family plan, your insurance may pay for 100 percent of covered medical expenses for the rest of the plan year.

If youplan to go to the doctor, need medication or have been recommended for surgery, call your insurance provider or go online to see what your plan covers. You can choose the best doctor for your needs, understand your options and prevent yourself from being blindsided by medical expenses.

Most doctors require a phone call for an appointment, although some may provide online scheduling as well. Be sure to have your insurance card with you when you set an appointment, and to bring it with you to the actual appointment. They need the ID numbers to verify your coverage, and will usually make a copy of the card for their files so you don't have to show it again unless your insurance changes.

When you call, let them know if you're a new patient, as this will require you to complete some paperwork for your first visit. Tell them the reason for your visit, such as your symptoms if you're feeling sick. It's also important to inform them if you have Medicaid and to find out if you need to bring anything to the visit, like current medications or medical records.

From here, the receptionist will likely ask what dates and times work best for you. During your call, it's important to be honest about your symptoms and the reason for your visit. This information will help the doctor treat you and give him or her an idea of what to expect. Your appointment may progress faster as a result, and the doctor can come prepared with a list of options to better care for you.

Doctors see a number of patients in a day, sometimes in 15-minute increments in areas where the physicians are in high demand. This can leavelittle time for doctors to perform thorough examinations, and they can end up missing certain problem indicators. While some problems, like a cold or flu, can be diagnosedin this time, more complex ailments require attention, which takes up time. Reviews can illuminate which doctors actively spend the necessary time with their patients and which ones are pressed against the clock to meet demand.

Surgery has some more dire risks attached to it, so be sure to talk to your surgeon about the potential issues that can come up as a result of your procedure. If a patient has a reaction to anesthesia, it can cause very serious complications, but this is an uncommon occurrence. Blood clots can be a significant problem aftersurgery, often caused by inactivity during recovery. Infections, numbness, scarring, swelling and death are all possible, but the likelihood of these issueswill vary depending on the type of surgery you're undergoing. Talk to your doctor about your concerns and your risk potential.

Surgery affects people in different ways, but as you begin to emerge from anesthesia, you'll want to alert your nurse to any issues you may have. The nurse will tell you how the procedure went, what effect it will have on your condition, what to expect when you get home and how long it will take to getback to normal. If you start feeling pain, the nurse may give you medication to stop it from getting worse. When possible, it's also advised to move around to avoid blood clots from developing in your legs. This can be as simple as occasionally flexing your knee or rotating your foot.

Some surgeries are outpatient procedures, where people are released the same day. For major surgeries, patients may stay at the hospital for a few days to be monitored and address any concerns before being sent home. Discuss with your surgeon the projected length of the hospital stayand what you need to bring.

Your recovery time and follow-up expectations will vary depending on your procedure. For example, you can be expected to be on your feet within a few days of having your wisdom teeth taken out, but it may be weeks before you have fully recovered from a broken foot or heart-valve surgery. Your surgeon will give you a list of things that you'll need to do during this time, including what medications to take and when you'll be able to get back to work and other activities.

Every surgery will have a follow-up call or appointment to discuss your recovery and allow you to ask any questions about unusual symptoms or changes in your overall health. If you have a major operation, like heart surgery, it's important to make regular checkupswith your doctor or a specialist to ensure that everything is normal. Visiting a doctor will help deter infection and verify that everything is healing as expected. These appointments will give you peace of mind about your state of health and ensure that any issues are caught early on.

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The physicians and staff of North State Medical Group, P.A. would like to thank you for choosing us to meet your medical needs. Our website should help answer any questions you may have about our practice.

Our commitment is to consistently provide the highest quality and most up-to-date care possible. It is our goal to provide comprehensive care to your entire family. If a health problem should arise that fall outside our specialty, we will assist you in locating an appropriate specialist and work closely with them to ensure your complete satisfaction.

We offer two locations for your convenience. To schedule an appointment at one of our offices, please see the phone numbers below or visit our Locations page.

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Dr. Gerald Ahigian and Dr. Susane Habashi-Ahigian

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This is a wonderful place to receive care from. The doctors and nurses are very compassionate and make you feel very comfortable.

Melinda

These doctors have taken care of my in-laws for about fifteen years and my in laws, and now we, love them. Doctors Susane and Gerald are always glad to take all the time I need to discuss anything that I feel is important. They have listened to my side of the story, and what I think is wrong with me and they do not immediately discredit my ability to judge my problem. . . .They do not rush their patients in and out. If I have to wait longer than 20 minutes, it is rare, but I dont care because I know that I will receive the same lengthy, courteous, professional treatment.

K Douthit

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Considering a Masters in Biotechnology Program or reviewing options for Masters Degrees in Biotechnology? A Masters in Biotechnology can openupexciting

Biotechnology is a challenging field that can involve a number of facets of both science and business or law. Many biotechnology master's degree programs focus on aspects of biology, cell biology, chemistry, or biological or chemical engineering. In general, biotechnology degrees involve research whether they are at a Masters or PhD level.

Scientific understanding is rapidly evolving, particularly in areas of cellular and molecular systems. Biotechnology master's students can therefore enjoy rich study opportunities particularly in fields such as genetic engineering, the Human Genome project, the production of new medicinal products, and research into the relationship between genetic malfunction and the origin of disease. These are just a few of the many areas that biotechnology students have the opportunity to explore today.

Another focus of biotechnology masters programs may be to equip students with the combination of science and business knowledge they need to help produce products and move them toward production. Today's complex business environment and government regulations require many steps and people with the ability to both understand and help produce new scientific technologies as well as get them approved and be able to market them.

Master degrees in biotechnology might prepare students to pursue careers in a variety of industries. While many students go on to further research or academic positions, there may also be some demand for biotechnologists outside of academia, both in the government and private sectors. Biotechnologists might pursue careers in anything from research to applied science and manufacturing. Those with specializations in business aspects of biotechnology may be qualified to pursue management positions within organizations attempting to produce and market new biotechnology.

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Masters in Biotechnology Programs and Degrees in Biotechnology

Biotechnology has proven to be an important tool for better sustainability and food security. It helps farmers grow more food while improving the environment. For example, biotechnology reduces the use of costly inputs and improves weed management, allowing farmers to reduce tillage for better soil, water and air quality. Today, roughly 90 percent of corn, cotton and soybeans grown in the U.S. have been improved through biotechnology, and farmers are choosing biotech traits when growing other crops such as alfalfa, sugarbeets and canola.

Despite rapid adoption by farmers and a strong scientific consensus that biotechnology does not pose health and environmental risks, regulatory burdens are slowing research and innovation of new biotech traits and are starting to reduce U.S. farmers international competitive advantage. In addition, activist groups routinely threaten the availability of new traits by blocking science-based regulatory decisions, filing lawsuits and advocating for labeling mandates.

GM crops require less water and fewer chemical applications than conventional crops, and they are better able to survive drought, weeds, and insects.

U.S. agriculture will maintain its competitive advantage in world markets only if we continue to support innovations in technology and grasp opportunities for future biotech products.

To improve regulation of biotechnology, Farm Bureau supports:

Farm Bureau encourages efforts to educate farmers to be good stewards of biotech crops to preserve accessand marketability.

Farm Bureau believes agricultural products grown using approved biotechnology should not be subject to mandatory labeling. We supportexisting FDA labeling policies and opposestate policies on biotech labeling, identification, use and availability.

On July 29, 2016 the president signed S. 764, the National Bioengineered Food Disclosure Standard, into law. While not perfect, S. 764 was a compromise that Farm Bureau endorsed. The law creates a uniform standard for the disclosure of ingredients derived from bioengineering and allows food companies to provide that information through an on-package statement, symbol or electronic disclosure. It also created a strong federal preemption provision to protect interstate commerce and prevent state-by-state labeling laws and was effective on the date of enactment. USDA has two years to develop the disclosure standards and Farm Bureau will be an active participant in the rulemaking process.

Farm Bureau supports active involvement and leadership by the U.S. government in the development of international standards for biotechnology, including harmonization of regulatory standards, testing and LLP policies.

This resource can help set the record straight on GMOs, to correct misinformation and show why biotechnology is so important to agriculture.

Benefits of Biotech Toolkit (PDF)

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Gene therapy delivers DNA into a patients cells to replace faulty or missing genes or adds new genes in an attempt to cure diseases or to make changes so the body is better able to fight off disease. The DNA for a gene or genes is carried into a patients cells by a delivery vehicle called a vector, typically a specially engineered virus. The vector then inserts the gene(s) into the cells' DNA.

Although gene therapy is relatively new and often still considered experimental, it can provide a cure for life-threatening diseases that dont respond well to other therapies (including immunodeficiencies, metabolic disorders, and relapsed cancers) and for acute conditions that currently rely on complex and expensive life-long medication and management (such as sickle cell disease and hemophilia).

Our Gene Therapy Clinical Trials

Learn more about our gene therapy clinical trials

Dana-Farber/Boston Childrens has one the most extensive and long-running pediatric gene therapy programs in the world. Since 2010, we have treated 25 patients from 11 countries through eight gene therapy clinical trials.

Why choose Dana-Farber/Boston Childrens:

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Lamarckism (or Lamarckian inheritance) is the idea that an organism can pass on characteristics that it has acquired during its lifetime to its offspring (also known as heritability of acquired characteristics or soft inheritance). It is named after the French biologist Jean-Baptiste Lamarck (17441829), who incorporated the action of soft inheritance into his evolutionary theories as a supplement to his concept of an inherent progressive tendency driving organisms continuously towards greater complexity, in parallel but separate lineages with no extinction. Lamarck did not originate the idea of soft inheritance, which proposes that individual efforts during the lifetime of the organisms were the main mechanism driving species to adaptation, as they supposedly would acquire adaptive changes and pass them on to offspring.

When Charles Darwin published his theory of evolution by natural selection in On the Origin of Species (1859), he continued to give credence to what he called "use and disuse inheritance," but rejected other aspects of Lamarck's theories. Later, Mendelian genetics supplanted the notion of inheritance of acquired traits, eventually leading to the development of the modern evolutionary synthesis, and the general abandonment of the Lamarckian theory of evolution in biology. Despite this abandonment, interest in Lamarckism has continued as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[1][2][3][4][5] However, this remains controversial as science historians have asserted that it is inaccurate to describe transgenerational epigenetic inheritance as a form of Lamarckism.[6][7][8][9]

Between 1794 and 1796 Erasmus Darwin wrote Zoonomia suggesting "that all warm-blooded animals have arisen from one living filament... with the power of acquiring new parts" in response to stimuli, with each round of "improvements" being inherited by successive generations.[10] Subsequently, Jean-Baptiste Lamarck repeated in his Philosophie Zoologique of 1809 the folk wisdom that characteristics which were "needed" were acquired (or diminished) during the lifetime of an organism then passed on to the offspring. He incorporated this mechanism into his thoughts on evolution, seeing it as resulting in the adaptation of life to local environments.

Lamarck founded a school of French Transformationism which included tienne Geoffroy Saint-Hilaire, and which corresponded with a radical British school of anatomy based in the extramural anatomy schools in Edinburgh, Scotland, which included the surgeon Robert Knox and the comparative anatomist Robert Edmond Grant. In addition, the Regius Professor of Natural History at the University of Edinburgh, Robert Jameson, was the probable author of an anonymous paper in 1826 praising "Mr. Lamarck" for explaining how the higher animals had "evolved" from the "simplest worms"this was the first use of the word "evolved" in a modern sense. As a young student, Charles Darwin was tutored by Grant, and worked with him on marine creatures.

The Vestiges of the Natural History of Creation, authored by Robert Chambers in St Andrews, Scotland, and published anonymously in England in 1844, proposed a theory which combined radical phrenology with Lamarckism, causing political controversy for its radicalism and unorthodoxy, but exciting popular interest and preparing a huge and prosperous audience for Darwin.

Darwin's On the Origin of Species proposed natural selection as the main mechanism for development of species, but did not rule out a variant of Lamarckism as a supplementary mechanism.[11] Darwin called his Lamarckian hypothesis pangenesis, and explained it in the final chapter of his book The Variation of Animals and Plants under Domestication (1868), after describing numerous examples to demonstrate what he considered to be the inheritance of acquired characteristics. Pangenesis, which he emphasised was a hypothesis, was based on the idea that somatic cells would, in response to environmental stimulation (use and disuse), throw off 'gemmules' or 'pangenes' which travelled around the body (though not necessarily in the bloodstream). These pangenes were microscopic particles that supposedly contained information about the characteristics of their parent cell, and Darwin believed that they eventually accumulated in the germ cells where they could pass on to the next generation the newly acquired characteristics of the parents. Darwin's half-cousin, Francis Galton, carried out experiments on rabbits, with Darwin's cooperation, in which he transfused the blood of one variety of rabbit into another variety in the expectation that its offspring would show some characteristics of the first. They did not, and Galton declared that he had disproved Darwin's hypothesis of pangenesis, but Darwin objected, in a letter to the scientific journal Nature, that he had done nothing of the sort, since he had never mentioned blood in his writings. He pointed out that he regarded pangenesis as occurring in Protozoa and plants, which have no blood.[12]

The identification of Lamarckism with the inheritance of acquired characteristics is regarded by some as an artifact of the subsequent history of evolutionary thought, repeated in textbooks without analysis. American paleontologist and historian of science Stephen Jay Gould wrote that in the late 19th century, evolutionists "re-read Lamarck, cast aside the guts of it ... and elevated one aspect of the mechanicsinheritance of acquired charactersto a central focus it never had for Lamarck himself."[13] He argued that "the restriction of 'Lamarckism' to this relatively small and non-distinctive corner of Lamarck's thought must be labelled as more than a misnomer, and truly a discredit to the memory of a man and his much more comprehensive system."[14] Gould advocated defining "Lamarckism" more broadly, in line with Lamarck's overall evolutionary theory.

Lamarck incorporated two ideas into his theory of evolution, in his day considered to be generally true. The first was the idea of use versus disuse; he theorized that individuals lose characteristics they do not require, or use, and develop characteristics that are useful. His second point was to argue that the acquired traits were heritable. Examples of what is traditionally called "Lamarckism" would include the idea that when giraffes stretch their necks to reach leaves high in trees (especially Acacias), they strengthen and gradually lengthen their necks. These giraffes have offspring with slightly longer necks (also known as "soft inheritance"). Similarly, a blacksmith, through his work, strengthens the muscles in his arms, and thus his sons will have similar muscular development when they mature.

Lamarck stated the following two laws:

English translation:

In essence, a change in the environment brings about change in "needs" (besoins), resulting in change in behavior, bringing change in organ usage and development, bringing change in form over timeand thus the gradual transmutation of the species.

However, as historians of science such as Michael Ghiselin and Stephen Jay Gould have pointed out, none of these views were original to Lamarck.[17][18] On the contrary, Lamarck's contribution was a systematic theoretical framework for understanding evolution. He saw evolution as comprising two processes;

The idea that germline cells contain information that passes to each generation unaffected by experience and independent of the somatic (body) cells, came to be referred to as the Weismann barrier, and is frequently quoted as putting a final end to Lamarckism and theory of inheritance of acquired characteristics.

August Weismann conducted the experiment of removing the tails of 68 white mice, repeatedly over five generations, and reporting that no mice were born in consequence without a tail or even with a shorter tail. He stated that "901 young were produced by five generations of artificially mutilated parents, and yet there was not a single example of a rudimentary tail or of any other abnormality in this organ."[19]

However, the experiment has been questioned in relationship to Lamarck's hypothesis as it did not address the use and disuse of characteristics in response to the environment. Biologist Peter Gauthier noted that:

Can Weismann's experiment be considered a case of disuse? Lamarck proposed that when an organ was not used, it slowly, and very gradually atrophied. In time, over the course of many generations, it would gradually disappear as it was inherited in its modified form in each successive generation. Cutting the tails off mice does not seem to meet the qualifications of disuse, but rather falls in a category of accidental misuse... Lamarck's hypothesis has never been proven experimentally and there is no known mechanism to support the idea that somatic change, however acquired, can in some way induce a change in the germplasm. On the other hand it is difficult to disprove Lamarck's idea experimentally, and it seems that Weismann's experiment fails to provide the evidence to deny the Lamarckian hypothesis, since it lacks a key factor, namely the willful exertion of the animal in overcoming environmental obstacles.[20]

Science historian Michael Ghiselin also considers the Weismann tail-chopping experiment to have no bearing on the Lamarckian hypothesis:

The acquired characteristics that figured in Lamarck's thinking were changes that resulted from an individual's own drives and actions, not from the actions of external agents. Lamarck was not concerned with wounds, injuries or mutilations, and nothing that Lamarck had set forth was tested or "disproven" by the Weismann tail-chopping experiment.[17]

The period of the history of evolutionary thought between Darwin's death in the 1880s, and the foundation of population genetics in the 1920s and beginnings of modern evolutionary synthesis in the 1930s, is called the eclipse of Darwinism by some historians of science. During that time many scientists and philosophers accepted the reality of evolution but doubted whether natural selection was the main evolutionary mechanism.[21]

Among the most popular alternatives were theories involving the inheritance of characteristics acquired during an organism's lifetime. Scientists who felt that such Lamarckian mechanisms were the key to evolution were called neo-Lamarckians and included the British botanist George Henslow (18351925), who studied the effects of environmental stress on the growth of plants, in the belief that such environmentally-induced variation might explain much of plant evolution, and the American entomologist Alpheus Spring Packard, Jr., who studied blind animals living in caves and wrote a book in 1901 about Lamarck and his work.[22][23]

Also included were a number of paleontologists like Edward Drinker Cope and Alpheus Hyatt, who felt that the fossil record showed orderly, almost linear, patterns of development that they felt were better explained by Lamarckian mechanisms than by natural selection. Some people, including Cope and the Darwin critic Samuel Butler, felt that inheritance of acquired characteristics would let organisms shape their own evolution, since organisms that acquired new habits would change the use patterns of their organs, which would kick-start Lamarckian evolution. They considered this philosophically superior to Darwin's mechanism of random variation acted on by selective pressures. Lamarckism also appealed to those, like the philosopher Herbert Spencer and the German anatomist Ernst Haeckel, who saw evolution as an inherently progressive process.[22] The German zoologist Theodor Eimer combined Larmarckism with ideas about orthogenesis.[24]

With the development of the modern synthesis of the theory of evolution and a lack of evidence for a mechanism for acquiring and passing on new characteristics, or even their heritability, Lamarckism largely fell from favor. Unlike neo-Darwinism, the term neo-Lamarckism refers more to a loose grouping of largely heterodox theories and mechanisms that emerged after Lamarck's time, than to any coherent body of theoretical work.

In a series of experiments from 1869 to 1891, Charles-douard Brown-Squard cut the sciatic nerve of the leg and spinal cord in the dorsal regions of guinea pigs, causing an abnormal nervous condition resembling epilepsy; these were then bred and produced epileptic offspring.[25] Although some scientists considered this evidence for Lamarckian inheritance, the experiments were not Lamarckian, as they did not address the use and disuse of characteristics in response to the environment.[26] The results from the experiment were not duplicated by other scientists.[27] One explanation for the results was that they show a transmitted disease, and not evidence for the inheritance of an acquired characteristic.[28] Brown-Squard's experiments are now considered anomalous and alternative explanations have been suggested.[29]

The French botanist Gaston Bonnier, conducting experiments in the French Alps in 1884 and the Pyrenees in 1886, studied structural changes induced by growing plants at various altitudes and transplanting them to others. Bonnier believed he had proven acquired adaptive characteristics; however, he did not weed, cultivate, fertilize or protect his plant specimens from native vegetation. In the 1920s his experiments were analysed and attributed to genetic contamination rather than Lamarckian inheritance.[30]

In a series of experiments (in 1891, 1893 and 1895) on the action of light on the coloration of flatfish, the British marine biologist Joseph Thomas Cunningham (18591935) directed light upon the lower sides of flatfishes by means of a glass-bottomed tank placed over a mirror. He discovered the influence of light in producing pigments on the lower sides of flatfishes and gave his results a Lamarckian interpretation.[31][32][33] Other scientists wrote that Cunningham had received some definite results, but that they were open to more than one interpretation.[34] The geneticist William Bateson was not convinced that the cause of the increase in pigmentation was from the illumination. George Romanes wrote approvingly of Cunningham's interpretation.[35]Thomas Hunt Morgan criticized the experiments and did not believe the results were evidence for Lamarckism.[36]

In 1906, the philosopher Eugenio Rignano wrote a book, Sur La Transmissibilit Des Caractres Acquis, that argued for the inheritance of acquired characteristics.[37] He advanced a moderated Lamarckian hypothesis of inheritance known as "centro-epigenesis."[38][39] However, his views were controversial and not accepted by the majority in the scientific community.[40]

In a series of experiments from 1907 to 1910, William Lawrence Tower performed experiments on potato beetles which were said by Ernest MacBride to have provided evidence for the inheritance of acquired characteristics.[41] These were heavily criticized by William Bateson.[42] It was later suggested that his research may have been faked.[43] Tower claimed that the records of his experimental results had been lost in a fire.[44] The geneticist William E. Castle who visited Tower's laboratory was not impressed by the experimental conditions. He later concluded that Tower had faked his data. Castle found the fire suspicious and also Tower's claim that a steam leak in his greenhouse had destroyed all his beetle stocks.[45]

Experiments conducted by Gustav Tornier from 1907 to 1918 on goldfish and embryos of frogs and newts were supported by neo-Lamarckians such as Cunningham and MacBride as demonstrating the inheritance of acquired characteristics.[46][47] The abnormalities were interpreted as the result of an osmotic effect by other researchers.[48]

In the late 19th century, Frederick Merrifield exposed caterpillars and chrysalids to significantly high and low temperatures, and discovered permanent changes in some offspring's wing patterns. Swiss biologist Maximilian Rudolph Standfuss (18541917) led 30 years of intensive breeding experiments with European butterflies and after several generations, found similar preserved variations even generations after the cessation of exposing them to low temperatures.[49] Standfuss was a neo-Lamarckian and attributed the results of his experiments as direct changes to the environment.[50] In 1940, Richard Goldschmidt interpreted these results without invoking Lamarckian inheritance, and in 1998 Ernst Mayr wrote that results reported by Standfuss and others on the effects of abnormal temperatures on Lepidoptera are difficult to interpret.[51]

In 1910, the American zoologist Charles Rupert Stockard (18791939) tested the effects of alcohol intoxication on the offspring of pregnant guinea pigs. Stockard discovered that repeated alcohol intoxication in the guinea pigs produced defects and malformations in their offspring that was passed down to two or more generations. His results were challenged by the biologist Raymond Pearl who performed the same experiments with chickens.[52] Pearl discovered that the offspring of the chickens that had been exposed to alcohol were not defected but were healthy. He attributed his findings to the detrimental effects of alcohol only on the eggs and sperm which were already weak, the strong eggs and sperm were unaffected by alcohol intoxication. Pearl argued that his results had a Darwinian, not a Lamarckian explanation.[52]

The French zoologist Yves Delage in his book The Theories of Evolution (1912) reviewed experiments into Lamarckism concluded the evidence "is not of uniform value and is more or less open to criticism; very little of it is convincing... [due to] difficulties of experimentation and, above all, of interpretation."[53]

In a series of experiments, Francis Bertody Sumner (18741945) reared several generations of white mice under different conditions of temperature and relative humidity.[54] Sumner discovered that the white mice at 20C to 30C developed longer bodies, tails and hind feet which were also transmitted to their offspring over a number of generations, however, later results were not entirely consistent and the experiments ended in uncertainty.[55]

Between 1918 and 1924, two American scientists Michael F. Guyer and Elizabeth A. Smith performed experiments in which fowl serum antibodies for rabbit lens-protein were injected into pregnant rabbits which resulted in defects in the eyes of some of their offspring that were inherited through eight generations.[56] Their experiments were criticized and were not repeated by other scientists.[57]

In the 1920s, experiments by Paul Kammerer on amphibians, particularly the midwife toad, appeared to find evidence supporting Lamarckism. However, his specimens with supposedly acquired black foot-pads were found to have been tampered with. In The Case of the Midwife Toad (1971), author and journalist Arthur Koestler surmised that the tampering had been done by a Nazi sympathiser to discredit Kammerer for his political views, and that his research might actually have been valid. However, most biologists believe that Kammerer was a fraud, and even among those who believe he was honest, most believe that he misinterpreted the results of his experiments.[58]

During the 1920s, Harvard University researcher William McDougall studied the abilities of rats to correctly solve mazes. He found that offspring of rats that had learned the maze were able to run it faster. The first rats would get it wrong 165 times before being able to run it perfectly each time, but after a few generations it was down to 20. McDougall attributed this to some sort of Lamarckian evolutionary process.[59]Oscar Werner Tiegs and Wilfred Eade Agar later showed McDougall's results to be incorrect, caused by poor experimental controls.[60][61]Peter Medawar wrote that "careful and extensive repetitions of McDougall's research failed altogether to confirm it. His work therefore becomes an exhibit in the capacious ill-lit museum of unreproducible phenomena."[62]

In the 1920s, John William Heslop-Harrison conducted experiments on the peppered moth, claiming to have evidence for the inheritance of acquired characteristics. Other scientists failed to replicate his results.[63][64] The Russian physiologist Ivan Pavlov claimed to have observed a similar phenomenon in white mice being subject to a conditioned reflex experiment involving food and the sound of a bell. He wrote that with each generation, the mice became easier to condition. In 1926, Pavlov announced that there had been a fatal flaw in his experiment and retracted his claim to have demonstrated Lamarckian inheritance.[65] Other researchers were also unable to replicate his results.[66]

In other experiments, Coleman Griffith (1920, 1922) and John Detlefson (1923, 1925) reared rats in cages on a rotating table for three months. The rats adapted to the rotating condition to such an extent that when the rotation was stopped they showed signs of disequilibration and other physiological conditions which were inherited for several generations.[67][68][69][70] In 1933, Roy Dorcus replicated their experiments but obtained different results as the rotated rats did not manifest any abnormalities of posture described by Griffith and Detlefson.[71] Other studies revealed that the same abnormalities could occur in rats without rotation if they were suffering from an ear infection thus the results were interpreted as a case of infection, not Lamarckian inheritance.[72]

In the 1930s, the German geneticist Victor Jollos (18871941) in a series of experiments claimed evidence for inherited changes induced by heat treatment in Drosophila melanogaster.[73] His experiments were described as Lamarckian. However, Jollos was not an advocate of Lamarckian evolution and attributed the results from his experiments as evidence for directed mutagenesis. American scientists were unable to replicate his results.[74]

The British anthropologist Frederic Wood Jones and the South African paleontologist Robert Broom supported a neo-Lamarckian view of human evolution as opposed to the Darwinian view. The German anthropologist Hermann Klaatsch relied on a neo-Lamarckian model of evolution to try and explain the origin of bipedalism. Neo-Lamarckism remained influential in biology until the 1940s when the role of natural selection was reasserted in evolution as part of the modern evolutionary synthesis.[75]

Herbert Graham Cannon, a British zoologist, defended Lamarckism in his 1959 book Lamarck and Modern Genetics.[76]

In the 1960s, "biochemical Lamarckism" was advocated by the embryologist Paul Wintrebert.[77]

In the 1970s, Australian immunologist Edward J. Steele and colleagues proposed a neo-Lamarckian mechanism to try to explain why homologous DNA sequences from the VDJ gene regions of parent mice were found in their germ cells and seemed to persist in the offspring for a few generations. The mechanism involved the somatic selection and clonal amplification of newly acquired antibody gene sequences that were generated via somatic hypermutation in B-cells. The messenger RNA (mRNA) products of these somatically novel genes were captured by retroviruses endogenous to the B-cells and were then transported through the bloodstream where they could breach the soma-germ barrier and retrofect (reverse transcribe) the newly acquired genes into the cells of the germ line. Although Steele was advocating this theory for the better part of two decades, little more than indirect evidence was ever acquired to support it. An interesting attribute of this idea is that it strongly resembles Darwin's own theory of pangenesis, except in the soma to germ line feedback theory, pangenes are replaced with realistic retroviruses.[78] Regarding Steele's research, historian of biology Peter J. Bowler wrote, "his work was bitterly criticized at the time by biologists who doubted his experimental results and rejected his hypothetical mechanism as implausible."[79]

Neo-Lamarckism was dominant in French biology for more than a century. French scientists who supported neo-Lamarckism included Edmond Perrier (18441921), Alfred Giard (18461908), Gaston Bonnier (18531922) and Pierre-Paul Grass (18951985).[80]

In 1987, Ryuichi Matsuda coined the term "pan-environmentalism" for his evolutionary theory which he saw as a fusion of Darwinism with neo-Lamarckism. He held that heterochrony is a main mechanism for evolutionary change and that novelty in evolution can be generated by genetic assimilation.[81][82] His views were criticized by Arthur M. Shapiro for providing no solid evidence for his theory. Shapiro noted that "Matsuda himself accepts too much at face value and is prone to wish-fulfilling interpretation."[82]

Within the discipline of history of technology, Lamarckism has been used in linking cultural development to human evolution by classifying artefacts as extensions of human anatomy: in other words, as the acquired cultural characteristics of human beings. Ben Cullen has shown that a strong element of Lamarckism exists in sociocultural evolution.[83]

A form of Lamarckism was revived in the Soviet Union of the 1930s when Trofim Lysenko promoted Lysenkoism which suited the ideological opposition of Joseph Stalin to genetics. This ideologically driven research influenced Soviet agricultural policy which in turn was later blamed for crop failures.[84]

Neo-Lamarckian versions of evolution were widespread in the late 19th century. The idea that living things could to some degree choose the characteristics that would be inherited allowed them things to be in charge of their own destiny as opposed to the Darwinian view, which made them puppets at the mercy of the environment. Such ideas were more popular than natural selection in the late 19th century as it made it possible for biological evolution to fit into a framework of a divine or naturally willed plan, thus the neo-Lamarckian view of evolution was often advocated by proponents of orthogenesis.[85] According to Peter J. Bowler:

One of the most emotionally compelling arguments used by the neo-Lamarckians of the late nineteenth century was the claim that Darwinism was a mechanistic theory which reduced living things to puppets driven by heredity. The selection theory made life into a game of Russian roulette, where life or death was predetermined by the genes one inherited. The individual could do nothing to mitigate bad heredity. Lamarckism, in contrast, allowed the individual to choose a new habit when faced with an environmental challenge and shape the whole future course of evolution.[86]

Supporters of neo-Lamarckism such as George Bernard Shaw and Arthur Koestler claimed that Lamarckism is more humane and optimistic than Darwinism.[87]

George Gaylord Simpson in his book Tempo and Mode in Evolution (1944) claimed that experiments in heredity have failed to corroborate any Lamarckian process.[88] Simpson noted that neo-Lamarckism "stresses a factor that Lamarck rejected: inheritance of direct effects of the environment" and neo-Lamarckism is closer to Darwin's pangenesis than Lamarck's views.[89] Simpson wrote, "the inheritance of acquired characters, failed to meet the tests of observation and has been almost universally discarded by biologists."[90]

Botanist Conway Zirkle pointed out that Lamarck did not originate the hypothesis that acquired characters were heritable, therefore it is incorrect to refer to it as Lamarckism:

What Lamarck really did was to accept the hypothesis that acquired characters were heritable, a notion which had been held almost universally for well over two thousand years and which his contemporaries accepted as a matter of course, and to assume that the results of such inheritance were cumulative from generation to generation, thus producing, in time, new species. His individual contribution to biological theory consisted in his application to the problem of the origin of species of the view that acquired characters were inherited and in showing that evolution could be inferred logically from the accepted biological hypotheses. He would doubtless have been greatly astonished to learn that a belief in the inheritance of acquired characters is now labeled "Lamarckian," although he would almost certainly have felt flattered if evolution itself had been so designated.[91]

Peter Medawar wrote regarding Lamarckism, "very few professional biologists believe that anything of the kind occursor can occurbut the notion persists for a variety of nonscientific reasons." Medawar stated there is no known mechanism by which an adaption acquired in an individual's lifetime can be imprinted on the genome and Lamarckian inheritance is not valid unless it excludes the possibility of natural selection but this has not been demonstrated in any experiment.[92]

Martin Gardner wrote in his book Fads and Fallacies in the Name of Science (1957):

A host of experiments have been designed to test Lamarckianism. All that have been verified have proved negative. On the other hand, tens of thousands of experiments reported in the journals and carefully checked and rechecked by geneticists throughout the world have established the correctness of the gene-mutation theory beyond all reasonable doubt... In spite of the rapidly increasing evidence for natural selection, Lamarck has never ceased to have loyal followers.... There is indeed a strong emotional appeal in the thought that every little effort an animal puts forth is somehow transmitted to his progeny.[93]

According to Ernst Mayr, any Lamarckian theory involving the inheritance of acquired characters has been refuted as "DNA does not directly participate in the making of the phenotype and that the phenotype, in turn, does not control the composition of the DNA."[94] Peter J. Bowler has written that although many early scientists took Lamarckism seriously, it was discredited by genetics in the early twentieth century.[95]

Forms of 'soft' or epigenetic inheritance within organisms have been suggested as neo-Lamarckian in nature by such scientists as Eva Jablonka and Marion J. Lamb. In addition to 'hard' or genetic inheritance, involving the duplication of genetic material and its segregation during meiosis, there are other hereditary elements that pass into the germ cells also.[96] These include things like methylation patterns in DNA and chromatin marks, both of which regulate the activity of genes. These are considered Lamarckian in the sense that they are responsive to environmental stimuli and can differentially affect gene expression adaptively, with phenotypic results that can persist for many generations in certain organisms.[97]

Jablonka and Lamb have called for an extended evolutionary synthesis. They have argued that there is evidence for Lamarckian epigenetic control systems causing evolutionary changes and the mechanisms underlying epigenetic inheritance can also lead to saltational changes that reorganize the epigenome.[98]

Interest in Lamarckism has increased, as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[96] A 2009 study examined foraging behavior in chickens as a function of stress:

Transmissions of information across generations which does not involve traditional inheritance of DNA-sequence alleles is often referred to as soft inheritance [99] or "Lamarckian inheritance."[100]

The study concluded:

Our findings suggest that unpredictable food access caused seemingly adaptive responses in feeding behavior, which may have been transmitted to the offspring by means of epigenetic mechanisms, including regulation of immune genes. This may have prepared the offspring for coping with an unpredictable environment.[100]

The evolution of acquired characteristics has also been shown in human populations who have experienced starvation, resulting in altered gene function in both the starved population and their offspring.[101] The process of DNA methylation is thought to be behind such changes.

In October 2010, further evidence linking food intake to traits inherited by the offspring were shown in a study of rats conducted by several Australian universities.[102] The study strongly suggested that fathers can transfer a propensity for obesity to their daughters as a result of the fathers' food intake, and not their genetics (or specific genes), prior to the conception of the daughter. A "paternal high-fat diet" was shown to cause cell dysfunction in the daughter, which in turn led to obesity for the daughter. Felicia Nowak, et al. reported at the Endocrine Society meeting in June 2013 that obese male rats passed on the tendency to obesity to their male offspring.[103]

Several studies, one conducted by researchers at Massachusetts Institute of Technology and another by researchers at the Tufts University School of Medicine, have rekindled the debate once again. As reported in MIT Technology Review in February 2009, "The effects of an animal's environment during adolescence can be passed down to future offspring ... The findings provide support for a 200-year-old theory of evolution that has been largely dismissed: Lamarckian evolution, which states that acquired characteristics can be passed on to offspring."[104] A report investigating the inheritance of resistance to viral infection in the nematode Caenorhabditis elegans suggests that small RNA molecules may be inherited in a non-Mendelian fashion and provide resistance to infection.[105] More recent studies in C. elegans have revealed that progeny may inherit information regarding environmental challenges that the parent experienced, such as starvation, and that this epigenetic effect may persist for multiple generations.[106]

A study (Akimoto et al. 2007) on epigenetic inheritance in rice plants came to the conclusion that "gene expression is flexibly tuned by methylation, allowing plants to gain or lose particular traits which are heritable as far as methylation patterns of corresponding genes are maintained. This is in support of the concept of Lamarckian inheritance, suggesting that acquired traits are heritable."[107] Another study (Sano, 2010) wrote that observations suggest that acquired traits are heritable in plants as far as the acquired methylation pattern is stably transmitted which is consistent with Lamarckian evolution.[108] Handel and Ramagopalan found that there is evidence that epigenetic alterations such as DNA methylation and histone modifications are transmitted transgenerationally as a mechanism for environmental influences to be passed from parents to offspring. According to Handel and Romagopalan "epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution."[109]

In their book An Introduction to Zoology (2013), Joseph Springer and Dennis Holley wrote:

Lamarck and his ideas were ridiculed and discredited. In a strange twist of fate, Lamarck may have the last laugh. Epigenetics, an emerging field of genetics, has shown that Lamarck may have been at least partially correct all along. It seems that reversible and heritable changes can occur without a change in DNA sequence (genotype) and that such changes may be induced spontaneously or in response to environmental factorsLamarck's "acquired traits." Determining which observed phenotypes are genetically inherited and which are environmentally induced remains an important and ongoing part of the study of genetics, developmental biology, and medicine.[110]

Eugene Koonin has written that the prokaryotic CRISPR system and Piwi-interacting RNA could be classified as Lamarckian and came to the conclusion that "Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment."[111]

A study in 2013 reported that mutations caused by a father's lifestyle can be inherited by his children through multiple generations.[112] A study from Lund University in Sweden showed that exercise changes the epigenetic pattern of genes that affect fat storage in the body.[113]

Commenting on this, Charlotte Ling explained:

The cells of the body contain DNA, which contains genes. We inherit our genes and they cannot be changed. The genes, however, have 'methyl groups' attached which affect what is known as 'gene expression' whether the genes are activated or deactivated. The methyl groups can be influenced in various ways, through exercise, diet and lifestyle, in a process known as 'DNA methylation'.[114]

A 2013 study published in Nature Neuroscience reported that mice trained to fear the smell of a chemical called acetophenone passed their fear onto at least two generations.[115][116] The science magazine New Scientist commented on the study saying, "While it needs to be corroborated, this finding seems consistent with Lamarckian inheritance. It is, however, based on epigenetics: changes that tweak the action of genes, not the genes themselves. So it fits with natural selection and may yet give Lamarck's name a sheen of respectability."[117]

Guy Barry wrote that Darwin's hypothesis pangenesis coupled with "Lamarckian somatic cell-derived epigenetic modifications" and de novo RNA and DNA mutations can explain the evolution of the human brain.[118]

Lamarckian elements also appear in the hologenome theory of evolution.[119]

The significance of epigenetic inheritance to the evolutionary process is uncertain. Critics assert that epigenetic inheritance modifications are not inherited past two or three generations, so are not a stable basis for evolutionary change.[122][123] According to a recent review in 2015, "there are no reported epigenetic marks transmitted via the male germ line during more than three generations."[122]

The evolutionary biologist T. Ryan Gregory contends that epigenetic inheritance should not be considered Lamarckian. According to Gregory, Lamarck did not claim the environment imposed direct effects on organisms. Instead, Lamarck "argued that the environment created needs to which organisms responded by using some features more and others less, that this resulted in those features being accentuated or attenuated, and that this difference was then inherited by offspring." Gregory has stated that Lamarckian evolution in the context of epigenetics is actually closer to the view held by Darwin rather than by Lamarck.[6]

In a paper titled Weismann Rules! OK? Epigenetics and the Lamarckian Temptation (2007), David Haig writes that research into epigenetic processes does allow a Lamarckian element in evolution but the processes do not challenge the main tenets of the modern evolutionary synthesis as modern Lamarckians have claimed. Haig argued for the primary of DNA and evolution of epigenetic switches by natural selection.[124] Haig has also written there is a "visceral attraction" to Lamarckian evolution from the public and some scientists as it posits the world with a meaning, in which organisms can shape their own evolutionary destiny.[125]

American biologist Jerry Coyne has stated that "lots of studies show us that Lamarckian inheritance doesnt operate" and epigenetic changes are rarely passed on to future generations, thus do not serve as the basis of evolutionary change.[126] Coyne has also written:

Lamarckism is not a heresy, but simply a hypothesis that hasnt held up... If epigenetics in the second sense is so important in evolution, let us have a list of, say, a hundred adaptations of organisms that evolved in this Larmackian way as opposed to the old, boring, neo-Darwinian way involving inherited changes in DNA sequence... I cant think of a single entry for that list.[127]

Thomas Dickens and Qazi Rahman (2012) have written epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of natural selection and do not challenge the modern synthesis. Dickens and Rahman have taken issue with the claims of Eva Jablonka and Marion J. Lamb on Lamarckian epigenetic processes.[128]

Edith Heard and Robert Martienssen (2014) in a Cell review were not convinced that epigenetics has revived Lamarckism as there is no evidence epigenetic changes are passed on to successive generations in mammals. They concluded the characteristics that are thought to be the result of epigenetic inheritance may be caused by other factors such as behavioral changes, undetected mutations, microbiome alterations or the transmission of metabolites.[129]

In 2015, Khursheed Iqbal and colleagues discovered that although "endocrine disruptors exert direct epigenetic effects in the exposed fetal germ cells, these are corrected by reprogramming events in the next generation." Molecular biologist Emma Whitelaw has cited this study as an example of evidence disputing Lamarckian epigenetic inheritance.[130] Another critic recently argued that bringing back Lamarck in the context of epigenetics is misleading, commenting, "We should remember [Lamarck] for the good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works."[131]

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Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.

In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicine.

Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, mental retardation, autism, and mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics, teratogens, and prenatal diagnosis. Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for neurologic, endocrine, cardiovascular, pulmonary, ophthalmologic, renal, psychiatric, and dermatologic conditions.

In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, see the Human genome project) that have enabled an unprecedented understanding of genetic disorders.

Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders. Referrals are made to genetics clinics for a variety of reasons, including birth defects, developmental delay, autism, epilepsy, short stature, and many others. Examples of genetic syndromes that are commonly seen in the genetics clinic include chromosomal rearrangements, Down syndrome, DiGeorge syndrome (22q11.2 Deletion Syndrome), Fragile X syndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, and Williams syndrome.

In the United States, physicians who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG).[1] In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by the ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M.D. or D.O. degree (or their equivalent) and have completed a minimum of 24 months of training in an ACGME-accredited residency program in internal medicine, pediatrics, obstetrics and gynecology, or other medical specialty.[2]

Metabolic (or biochemical) genetics involves the diagnosis and management of inborn errors of metabolism in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates, amino acids, and lipids. Examples of metabolic disorders include galactosemia, glycogen storage disease, lysosomal storage disorders, metabolic acidosis, peroxisomal disorders, phenylketonuria, and urea cycle disorders.

Cytogenetics is the study of chromosomes and chromosome abnormalities. While cytogenetics historically relied on microscopy to analyze chromosomes, new molecular technologies such as array comparative genomic hybridization are now becoming widely used. Examples of chromosome abnormalities include aneuploidy, chromosomal rearrangements, and genomic deletion/duplication disorders.

Molecular genetics involves the discovery of and laboratory testing for DNA mutations that underlie many single gene disorders. Examples of single gene disorders include achondroplasia, cystic fibrosis, Duchenne muscular dystrophy, hereditary breast cancer (BRCA1/2), Huntington disease, Marfan syndrome, Noonan syndrome, and Rett syndrome. Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, and uniparental disomy.

Mitochondrial genetics concerns the diagnosis and management of mitochondrial disorders, which have a molecular basis but often result in biochemical abnormalities due to deficient energy production.

There exists some overlap between medical genetic diagnostic laboratories and molecular pathology.

Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, and risks in other family members, within the framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders. The precise role of the genetic counselor varies somewhat depending on the disorder.

Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism, brachydactyly (short fingers and toes), and hemophilia. Mathematical approaches were also devised and applied to human genetics. Population genetics was created.

Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in the 21st century.

The clinical setting in which patients are evaluated determines the scope of practice, diagnostic, and therapeutic interventions. For the purposes of general discussion, the typical encounters between patients and genetic practitioners may involve:

Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish a differential diagnosis and recommend appropriate testing. Increasingly, clinicians use SimulConsult, paired with the National Library of Medicine Gene Review articles, to narrow the list of hypotheses (known as the differential diagnosis) and identify the tests that are relevant for a particular patient. These tests might evaluate for chromosomal disorders, inborn errors of metabolism, or single gene disorders.

Chromosome studies are used in the general genetics clinic to determine a cause for developmental delay/mental retardation, birth defects, dysmorphic features, and/or autism. Chromosome analysis is also performed in the prenatal setting to determine whether a fetus is affected with aneuploidy or other chromosome rearrangements. Finally, chromosome abnormalities are often detected in cancer samples. A large number of different methods have been developed for chromosome analysis:

Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In the US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests:

Each cell of the body contains the hereditary information (DNA) wrapped up in structures called chromosomes. Since genetic syndromes are typically the result of alterations of the chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly inborn errors of metabolism, the mechanism of disease is well understood and offers the potential for dietary and medical management to prevent or reduce the long-term complications. In other cases, infusion therapy is used to replace the missing enzyme. Current research is actively seeking to use gene therapy or other new medications to treat specific genetic disorders.

In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in the hypothetical example:

Compound "A" is metabolized to "B" by enzyme "X", compound "B" is metabolized to "C" by enzyme "Y", and compound "C" is metabolized to "D" by enzyme "Z". If enzyme "Z" is missing, compound "D" will be missing, while compounds "A", "B", and "C" will build up. The pathogenesis of this particular condition could result from lack of compound "D", if it is critical for some cellular function, or from toxicity due to excess "A", "B", and/or "C". Treatment of the metabolic disorder could be achieved through dietary supplementation of compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with a medication that promoted disposal of excess "A", "B", or "C". Another approach that can be taken is enzyme replacement therapy, in which a patient is given an infusion of the missing enzyme.

Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including galactosemia, phenylketonuria (PKU), maple syrup urine disease, organic acidurias and urea cycle disorders. Such restrictive diets can be difficult for the patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders.

Medical approaches include enhancement of residual enzyme activity (in cases where the enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase, treatment with NTBC in Tyrosinemia to inhibit the production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders.

Certain lysosomal storage diseases are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include Gaucher disease, Fabry disease, Mucopolysaccharidoses and Glycogen storage disease type II. Such treatments are limited by the ability of the enzyme to reach the affected areas (the blood brain barrier prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders.

There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. It should be noted that the information included in this section applies to the typical pathways in the United States and there may be differences in other countries. US Practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics.

Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different from a typically laboratory test that provides a "snapshot" of an individual's health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns.

On 19 March 2015, scientists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited.[3][4][5][6] In April 2015 and April 2016, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[7][8][9] In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR and related techniques on condition that the embryos were destroyed within seven days.[10] In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit.[11]

The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the American Society of Human Genetics. The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis.

Medical genetics is now recognized as a distinct medical specialty in the U.S. with its own approved board (the American Board of Medical Genetics) and clinical specialty college (the American College of Medical Genetics). The College holds an annual scientific meeting, publishes a monthly journal, Genetics in Medicine, and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics.

The broad range of research in medical genetics reflects the overall scope of this field, including basic research on genetic inheritance and the human genome, mechanisms of genetic and metabolic disorders, translational research on new treatment modalities, and the impact of genetic testing

Basic research geneticists usually undertake research in universities, biotechnology firms and research institutes.

Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation influence group differences in health outcomes.[12][13][14] According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases.[15] Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model.[16] However, the generality of the model has not yet been established and, in some cases, is in doubt.[13][17][18] Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model.[19]

Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare.[20][21] Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry.[19][22] However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in the incidence of the disease.

The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background.[17][23][24][25] If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift.[26]

One area in which population categories can be important considerations in genetics research is in controlling for confounding between population substructure, environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied,[27] although the magnitude of this problem in genetic association studies is subject to debate.[28][29] Various methods have been developed to detect and account for population substructure,[30][31] but these methods can be difficult to apply in practice.[32]

Population substructure also can be used to advantage in genetic association studies. For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations.[33][34][35][36] Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.[37][38]

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Best Paper Award: 3 Biotech is supported by King Abdulaziz City for Science and Technology (KACST) in Saudi Arabia. Every year KACST awards the best paper with the KACST Medal and $5,000. The editors of 3 Biotech have elected the best paper among those published in 2011-2012 and 2012-2013.

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Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin

Authors: G. Devanand Venkatasubbu and colleagues at Anna University, India.

- The 2012-2013winning paper is: Stress influenced increase in phenolic content and radical scavenging capacity of Rhodotorula glutinis CCY 20-2-26 Authors: Raj Kumar Salar and colleagues at Chaudhary Devi Lal University, India.

Related subjects Agriculture - Biomaterials - Biotechnology - Cancer Research - Cell Biology - Systems Biology and Bioinformatics

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The genetic code is the set of rules by which information encoded within genetic material (DNA or mRNA sequences) is translated into proteins by living cells. Translation is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

The code defines how sequences of nucleotide triplets, called codons, specify which amino acid will be added next during protein synthesis. With some exceptions,[1] a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. Because the vast majority of genes are encoded with exactly the same code (see the RNA codon table), this particular code is often referred to as the canonical or standard genetic code, or simply the genetic code, though in fact some variant codes have evolved. For example, protein synthesis in human mitochondria relies on a genetic code that differs from the standard genetic code.

While the "genetic code" determines a protein's amino acid sequence, other genomic regions determine when and where these proteins are produced according to a multitude of more complex "gene regulatory codes".

Serious efforts to understand how proteins are encoded began after the structure of DNA was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins. With four different nucleotides, a code of 2 nucleotides would allow for only a maximum of 42 = 16 amino acids. A code of 3 nucleotides could code for a maximum of 43 = 64 amino acids.[2]

The Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases; Marshall Nirenberg and Heinrich J. Matthaei were the first to elucidate the nature of a codon in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine.[3] They thereby deduced that the codon UUU specified the amino acid phenylalanine. This was followed by experiments in Severo Ochoa's laboratory that demonstrated that the poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysine[4] and that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline.[5] Therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using different copolymers most of the remaining codons were then determined. Subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA (tRNA), the adapter molecule that facilitates the process of translating RNA into protein. This work was based upon earlier studies by Severo Ochoa, who received the Nobel Prize in Physiology or Medicine in 1959 for his work on the enzymology of RNA synthesis.[6]

Extending this work, Nirenberg and Philip Leder revealed the triplet nature of the genetic code and deciphered the codons of the standard genetic code. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, the components of cells that translate RNA into protein. Unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments.[7] In 1968, Khorana, Holley and Nirenberg received the Nobel Prize in Physiology or Medicine for their work.[8]

A codon is defined by the initial nucleotide from which translation starts and sets the frame for a run of uninterrupted triplets, which is known as an "open reading frame" (ORF). For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA, and CCC; and, if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. Every sequence can, thus, be read in its 5' 3' direction in three reading frames, each of which will produce a different amino acid sequence (in the given example, Gly-Lys-Pro, Gly-Asn, or Glu-Thr, respectively). With double-stranded DNA, there are six possible reading frames, three in the forward orientation on one strand and three reverse on the opposite strand.[9]:330 The actual frame from which a protein sequence is translated is defined by a start codon, usually the first AUG codon in the mRNA sequence.

In eukaryotes, ORFs in exons are often interrupted by introns.

Translation starts with a chain initiation codon or start codon. Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences such as the Shine-Dalgarno sequence in E. coli and initiation factors are also required to start translation. The most common start codon is AUG, which is read as methionine or, in bacteria, as formylmethionine. Alternative start codons depending on the organism include "GUG" or "UUG"; these codons normally represent valine and leucine, respectively, but as start codons they are translated as methionine or formylmethionine.[10]

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. "Amber" was named by discoverers Richard Epstein and Charles Steinberg after their friend Harris Bernstein, whose last name means "amber" in German.[11] The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme. Stop codons are also called "termination" or "nonsense" codons. They signal release of the nascent polypeptide from the ribosome because there is no cognate tRNA that has anticodons complementary to these stop signals, and so a release factor binds to the ribosome instead.[12]

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can affect the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low1 error in every 10100million basesdue to the "proofreading" ability of DNA polymerases.[14][15]

Missense mutations and nonsense mutations are examples of point mutations, which can cause genetic diseases such as sickle-cell disease and thalassemia respectively.[16][17][18] Clinically important missense mutations generally change the properties of the coded amino acid residue between being basic, acidic, polar or non-polar, whereas nonsense mutations result in a stop codon.[9]:266

Mutations that disrupt the reading frame sequence by indels (insertions or deletions) of a non-multiple of 3 nucleotide bases are known as frameshift mutations. These mutations usually result in a completely different translation from the original, and are also very likely to cause a stop codon to be read, which truncates the creation of the protein.[19] These mutations may impair the function of the resulting protein, and are thus rare in in vivo protein-coding sequences. One reason inheritance of frameshift mutations is rare is that, if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause death before the organism is viable.[20] Frameshift mutations may result in severe genetic diseases such as Tay-Sachs disease.[21]

Although most mutations that change protein sequences are harmful or neutral, some mutations have a beneficial effect on an organism.[22] These mutations may enable the mutant organism to withstand particular environmental stresses better than wild type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection.[23]Viruses that use RNA as their genetic material have rapid mutation rates,[24] which can be an advantage, since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system.[25] In large populations of asexually reproducing organisms, for example, E. coli, multiple beneficial mutations may co-occur. This phenomenon is called clonal interference and causes competition among the mutations.[26]

Degeneracy is the redundancy of the genetic code. This term was given by Bernfield and Nirenberg. The genetic code has redundancy but no ambiguity (see the codon tables below for the full correlation). For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example, the amino acid leucine is specified by YUR or CUN (UUA, UUG, CUU, CUC, CUA, or CUG) codons (difference in the first or third position indicated using IUPAC notation), while the amino acid serine is specified by UCN or AGY (UCA, UCG, UCC, UCU, AGU, or AGC) codons (difference in the first, second, or third position).[27]:102117:521522 A practical consequence of redundancy is that errors in the third position of the triplet codon cause only a silent mutation or an error that would not affect the protein because the hydrophilicity or hydrophobicity is maintained by equivalent substitution of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. NCN yields amino acid residues that are small in size and moderate in hydropathy; NAN encodes average size hydrophilic residues. The genetic code is so well-structured for hydropathy that a mathematical analysis (Singular Value Decomposition) of 12 variables (4 nucleotides x 3 positions) yields a remarkable correlation (C = 0.95) for predicting the hydropathy of the encoded amino acid directly from the triplet nucleotide sequence, without translation.[28][29] Note in the table, below, eight amino acids are not affected at all by mutations at the third position of the codon, whereas in the figure above, a mutation at the second position is likely to cause a radical change in the physicochemical properties of the encoded amino acid.

The frequency of codons, also known as codon usage bias, can vary from species to species with functional implications for the control of translation. The following codon usage table is for the human genome.[30]

While slight variations on the standard code had been predicted earlier,[31] none were discovered until 1979, when researchers studying human mitochondrial genes discovered they used an alternative code.[32] Many slight variants have been discovered since then,[33] including various alternative mitochondrial codes,[34] and small variants such as translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than a leucine in yeasts of the "CTG clade" (Candida albicans is member of this group).[35][36][37] Because viruses must use the same genetic code as their hosts, modifications to the standard genetic code could interfere with the synthesis or functioning of viral proteins.[38] However, some viruses (such as totiviruses) have adapted to the genetic code modification of the host.[39] In bacteria and archaea, GUG and UUG are common start codons, but in rare cases, certain proteins may use alternative start codons not normally used by that species.[33]

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending on associated signal sequences in the messenger RNA. For example, UGA can code for selenocysteine and UAG can code for pyrrolysine. Selenocysteine is now viewed as the 21st amino acid, and pyrrolysine is viewed as the 22nd.[33] Unlike selenocysteine, pyrrolysine encoded UAG is translated with the participation of a dedicated aminoacyl-tRNA synthetase.[40] Both selenocysteine and pyrrolysine may be present in the same organism.[41] Although the genetic code is normally fixed in an organism, the achaeal prokaryote Acetohalobium arabaticum can expand its genetic code from 20 to 21 amino acids (by including pyrrolysine) under different conditions of growth.[42]

Despite these differences, all known naturally occurring codes are very similar to each other, and the coding mechanism is the same for all organisms: three-base codons, tRNA, ribosomes, reading the code in the same direction and translating the code three letters at a time into sequences of amino acids.

Variant genetic codes used by an organism can be inferred by identifying highly conserved genes encoded in that genome, and comparing its codon usage to the amino acids in homologous proteins of other organisms. For example, the program FACIL[43] infers a genetic code by searching which amino acids in homologous protein domains are most often aligned to every codon. The resulting amino acid probabilities for each codon are displayed in a genetic code logo, that also shows the support for a stop codon.

The DNA codon table is essentially identical to that for RNA, but with U replaced by T.

The origin of the genetic code is a part of the question of the origin of life. Under the main hypothesis for the origin of life, the RNA world hypothesis, any model for the emergence of genetic code is intimately related to a model of the transfer from ribozymes (RNA enzymes) to proteins as the principal enzymes in cells. In line with the RNA world hypothesis, transfer RNA molecules appear to have evolved before modern aminoacyl-tRNA synthetases, so the latter cannot be part of the explanation of its patterns.[45]

A consideration of a hypothetical random genetic code further motivates a biochemical or evolutionary model for the origin of the genetic code. If amino acids were randomly assigned to triplet codons, there would be 1.51084 possible genetic codes to choose from.[46]:163 This number is found by calculating how many ways there are to place 21 items (20 amino acids plus one stop) in 64 bins, wherein each item is used at least once. [2] In fact, the distribution of codon assignments in the genetic code is nonrandom.[47] In particular, the genetic code clusters certain amino acid assignments. For example, amino acids that share the same biosynthetic pathway tend to have the same first base in their codons. This could be an evolutionary relic of early simpler genetic code with fewer amino acids, that later diverged to code for a larger set of amino acids.[48] It could also reflect steric and chemical properties that had another effect on the codon during its evolution. Amino acids with similar physical properties also tend to have similar codons,[49][50] reducing the problems caused by point mutations and mistranslations.[47]

Given the non-random genetic triplet coding scheme, it has been suggested that a tenable hypothesis for the origin of genetic code should address multiple aspects of the codon table such as absence of codons for D-amino acids, secondary codon patterns for some amino acids, confinement of synonymous positions to third position, a limited set of only 20 amino acids instead of a number closer to 64, and the relation of stop codon patterns to amino acid coding patterns.[51]

There are three main ideas for the origin of the genetic code, and many models belong to either one of them or to a combination thereof:[52]

Hypotheses for the origin of the genetic code have addressed a variety of scenarios:[56]

Since 2001, 40 non-natural amino acids have been added into protein by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl tRNA-synthetase pair to encode it with diverse physicochemical and biological properties in order to be used as a tool to exploring protein structure and function or to create novel or enhanced proteins.[71][72]

H. Murakami and M. Sisido have extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th (in vivo) codon.[73]

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Genetic code - Wikipedia

Journal of Biotechnology & Biomaterials is a peer reviewed journal which publishes high quality articles reporting original research, review, commentary, opinion, rapid communication, case report etc. on all aspects of Biotechnology and Biomaterials. Content areas include Plant/Animal/Microbial Biotechnology, Applied Biotechnology, Red/Medical Biotechnology, Green/Agricultural Biotechnology, Environmental Biotechnology, Blue/Marine Biotechnology, White/Industrial Biotechnology, Food Biotechnology, Orthopedic and Dental Biomaterials, Cardiovascular Biomaterials, Ophthalmologic Biomaterials, Bioelectrodes and Biosensors, Burn Dressings and Skin Substitutes, Sutures, Drug Delivery Systems etc. This Biotechnology Journal with highest impact factor offers Open Access option to meet the needs of authors and maximize article visibility.

The journal is an academic journal providing an opportunity to researchers and scientists to explore the advanced and latest research developments in the use of living organisms and bioprocesses in engineering, technology and medicine. The Journal of Biotechnology and Biomaterials is of highest standards in terms of quality and provides a collaborative open access platform to the scientists throughout the world in the field of Biotechnology and Biomaterials. Journal of Biotechnology and Biomaterials is a scholarly Open Access journal and aims to publish the most complete and reliable source of information on the advanced and very latest research topics.

The journal is using the Editorial Manager System for quality in the peer-review process. Editorial Manager System is an online submission and review system, where authors can submit manuscripts and track their progress. Reviewers can download manuscripts and submit their opinions. Editors can manage the whole submission, review, revise & publish process. Publishers can see what manuscripts are in the pipeline awaiting publication.

The Journal assures a 21 days rapid review process with international peer-review standards and with quality reviewers. E-mail is sent automatically to concerned persons when significant events occur. After publishing, articles are freely available through online without any restrictions or any other subscriptions to researchers worldwide.

Applied Biotechnology is gives the major opportunity to study science on the edge of technology, innovation and even science itself. Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more.

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Biomaterials are commonly used in various medical devices and systems such as drug delivery systems, hybrid organs, tissue cultures, synthetic skin, synthetic blood vessels, artificial hearts, screws, plates, cardiac pacemakers, wires and pins for bone treatments, total artificial joint implants, skull reconstruction, and dental and maxillofacial applications. Among various applications, the application of biomaterials in cardiovascular system is most significant. The use of cardiovascular biomaterials (CB) is subjected to its blood compatibility and its integration with the surrounding environment where it is implanted.

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Biomaterials are used daily in surgery, dental applications and drug delivery. Biomaterial implant is a construct with impregnated pharmaceutical products which can be placed into the body, that permits the prolonged release of a drug over an extended period of time. A biomaterial may also be an autograft, allograft or xenograft used as a transplant material.

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Animal Biotechnology covers the identification and manipulation of genes and their products, stressing applications in domesticated animals. Animals are used in many ways in biotechnology. Biotechnology provides new tools for improving human health and animal health and welfare and increasing livestock productivity. Biotechnology improves the food we eat - meat, milk and eggs. Biotechnology can improve an animals impact on the environment.

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A biomaterial is any surface, matter, or construct that interacts with biological systems. The biomaterial science is the study of biomaterials. Biomaterials science encloses elements of medicine, biology, chemistry, tissue engineering and materials science. Biomaterials derived from either nature or synthesized in the laboratory using a different typrs of chemicals utilizing metallic components, polymers, ceramics or composite materials. They are oftenly used for a medical application.

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Nanobiotechnology, nanobiology and bionanotechnology are terms that refer to the intersection of nanotechnology and biology. Bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies. This discipline helps to indicate the merger of biological research with various fields of nanotechnology. Concepts enhanced through nanobiology are nanodevices, nanoparticles, and nanoscale phenomena. Nanotechnology uses biological systems as the biological inspirations.

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Biocatalysis are used as natural catalysts, like protein enzymes, to perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task. Since biocatalysis deals with enzymes and microorganisms, it is historically classified separately from "homogeneous catalysis" and "heterogeneous catalysis". However, biocatalysis is simply a heterogeneous catalysis.

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Agricultural biotechnology is a collection of scientific techniques used to improve plants, animals and microorganisms. Based on an structure and characteristics of DNA, scientists have developed solutions to increase agricultural productivity. Scientists have learned how to move genes from one organism to another. This has been called genetic modification (GM), genetic engineering (GE) or genetic improvement (GI). Regardless of the name, the process allows the transfer of useful characteristics (such as resistance to a disease) into a plant, animal or microorganism by inserting genes from another organism.

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A biomolecule is any molecule which is present in living organisms, entails large macromolecules like proteins, lipids, polysaccharides, and nucleic acids, as well as small molecules include primary metabolites, secondary metabolites, and natural products. A common name for this class of material is biological materials. Nucleosides are molecules formed by attaching a nucleobase to a ribose or deoxyribose ring. Nucleosides can be phosphorylated by specific kinases in the cell, producing nucleotides.

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Industrial or white biotechnology uses enzymes and micro-organisms to make biobased products in sectors like chemicals, food and feed, detergents, paper and pulp, textiles and bioenergy (such as biofuels or biogas). It uses renewable raw materials and is one of the most promising, newest approaches towards lowering greenhouse gas emissions. Industrial biotechnology application has been proven to make significant contributions towards mitigating the impacts of climate change in these and other sectors.

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Session & Tracks

Track 1:Molecular Biotechnology

Molecular biotechnology is the use of laboratory techniques to study and modify nucleic acids and proteins for applications in areas such as human and animal health, agriculture, and the environment.Molecular biotechnologyresults from the convergence of many areas of research, such as molecular biology, microbiology,biochemistry, immunology, genetics, and cell biology. It is an exciting field fueled by the ability to transfer genetic information between organisms with the goal of understanding important biological processes or creating a useful product.

Related Conferences

11th World Congress onBiotechnology and Biotech IndustriesMeet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA; GlobalBiotechnology Congress2016, May 11th-14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA;BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil;Bio Pharm America 20158th Annual International Partnering Conference, September 15-17, 2015, Boston, MA, USA.

Track 2:Environmental Biotechnology

The biotechnology is applied and used to study the natural environment. Environmental biotechnology could also imply that one try to harness biological process for commercial uses and exploitation. It is "the development, use and regulation of biological systems for remediation of contaminated environment and forenvironment-friendly processes(green manufacturing technologies and sustainable development). Environmental biotechnology can simply be described as "the optimal use of nature, in the form of plants, animals, bacteria, fungi and algae, to producerenewable energy, food and nutrients in a synergistic integrated cycle of profit making processes where the waste of each process becomes the feedstock for another process".

Related Conferences

11th World Congress onBiotechnology and Biotech IndustriesMeet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA; GlobalBiotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & BiotechPatent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands

Track 3:Animal Biotechnology

It improves the food we eat - meat, milk and eggs. Biotechnology can improve an animals impact on the environment. Animalbiotechnologyis the use of science and engineering to modify living organisms. The goal is to make products, to improve animals and to developmicroorganismsfor specific agricultural uses. It enhances the ability to detect, treat and prevent diseases, 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).

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA;Global Biotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & BiotechPatent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkers in Diagnostics, Oct 07-08, 2015 Berlin, Germany, DEU.

Track 4:Medical Biotechnology and Biomedical Engineering

Medicine is by means of biotechnology techniques so much in diagnosing and treating dissimilar diseases. It also gives opportunity for the population to defend themselves from hazardous diseases. The pasture of biotechnology, genetic engineering, has introduced techniques like gene therapy, recombinant DNA technologyand polymerase chain retort which employ genes and DNA molecules to make adiagnosis diseasesand put in new and strong genes in the body which put back the injured cells. There are some applications of biotechnology which are live their part in the turf of medicine and giving good results.

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA;Global Biotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & Biotech Patent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkers in Diagnostics, Oct 07-08, 2015 Berlin, Germany, DEU.

Track 5:Agricultural Biotechnology

Biotechnology is being used to address problems in all areas of agricultural production and processing. This includesplant breedingto raise and stabilize yields; to improve resistance to pests, diseases and abiotic stresses such as drought and cold; and to enhance the nutritional content of foods. Modern agricultural biotechnology improves crops in more targeted ways. The best known technique is genetic modification, but the term agricultural biotechnology (or green biotechnology) also covers such techniques asMarker Assisted Breeding, which increases the effectiveness of conventional breeding.

Related Conferences

3rd GlobalFood Safety Conference, September 01-03, 2016, Atlanta USA; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 12thBiotechnology Congress, Nov 14-15, 2016, San Francisco, USA;Biologically Active Compoundsin Food, October 15-16 2015 Lodz, Poland; World Conference onInnovative Animal Nutrition and Feeding, October 15-17, 2015 Budapest, Hungary; 18th International Conference onFood Science and Biotechnology, November 28 - 29, 2016, Istanbul, Turkey; 18th International Conference on Agricultural Science, Biotechnology,Food and Animal Science, January 7 - 8, 2016, Singapore; International IndonesiaSeafood and Meat, 1517 October 2016, Jakarta, Indonesia.

Track 6:Industrial Biotechnology and Pharmaceutical Biotechnology

Industrial biotechnology is the application of biotechnology for industrial purposes, includingindustrial fermentation. The practice of using cells such as micro-organisms, or components of cells like enzymes, to generate industrially useful products in sectors such as chemicals, food and feed, detergents, paper and pulp, textiles andbiofuels. Industrial Biotechnology offers a premier forum bridging basic research and R&D with later-stage commercialization for sustainable bio based industrial and environmental applications.

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA; GlobalBiotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & BiotechPatent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkers in Diagnostics, Oct 07-08, 2015 Berlin, Germany, DEU.

Track 8:Microbial and Biochemical Technology

Microorganisms have been exploited for their specific biochemical and physiological properties from the earliest times for baking, brewing, and food preservation and more recently for producingantibiotics, solvents, amino acids, feed supplements, and chemical feedstuffs. Over time, there has been continuous selection by scientists of special strains ofmicroorganisms, based on their efficiency to perform a desired function. Progress, however, has been slow, often difficult to explain, and hard to repeat. Recent developments inmolecular biologyand genetic engineering could provide novel solutions to long-standing problems. Over the past decade, scientists have developed the techniques to move a gene from one organism to another, based on discoveries of how cells store, duplicate, and transfer genetic information.

Related conferences

3rdGlobal Food Safety Conference, September 01-03, 2016, Atlanta USA; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 12thBiotechnology Congress, Nov 14-15, 2016, San Francisco, USA;Biologically Active Compoundsin Food, October 15-16 2015 Lodz, Poland; World Conference onInnovative Animal Nutrition and Feeding, October 15-17, 2015 Budapest, Hungary; 18th International Conference onFood Science and Biotechnology, November 28 - 29, 2016, Istanbul, Turkey; 18th International Conference on Agricultural Science, Biotechnology,Food and Animal Science, January 7 - 8, 2016, Singapore; International IndonesiaSeafood and Meat, 1517 October 2016, Jakarta, Indonesia.

Track 9:Food Processing and Technology

Food processing is a process by which non-palatable and easily perishable raw materials are converted to edible and potable foods and beverages, which have a longer shelf life. Biotechnology helps in improving the edibility, texture, and storage of the food; in preventing the attack of the food, mainly dairy, by the virus likebacteriophage producing antimicrobial effect to destroy the unwanted microorganisms in food that cause toxicity to prevent the formation and degradation of other toxins andanti-nutritionalelements present naturally in food.

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA;Global Biotechnology Congress 2016, May 11th-14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA;BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil;Bio Pharm America 20158th Annual International Partnering Conference, September 15-17, 2015, Boston, MA, USA.

Track 10:Genetic Engineering and Molecular Biology

One kind of biotechnology is gene technology, sometimes called 'genetic engineering' or'genetic modification', where the genetic material of living things is deliberately altered to enhance or remove a particular trait and allow the organism to perform new functions. Genes within a species can be modified, or genes can be moved from one species to another. Genetic engineering has applications inmedicine, research, agriculture and can be used on a wide range of plants, animals and microorganisms. It resulted in a series of medical products. The first two commercially prepared products from recombinant DNA technology were insulin andhuman growth hormone, both of which were cultured in the E. coli bacteria.

The field of molecular biology overlaps with biology and chemistry and in particular, genetics and biochemistry. A key area of molecular biology concerns understanding how various cellular systems interact in terms of the way DNA, RNA and protein synthesis function.

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA;Global Biotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & BiotechPatent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkers in Diagnostics, Oct 07-http://world.biotechnologycongress.com/08, 2015 Berlin, Germany, DEU.

Track 11:Tissue Science and Engineering

Tissue engineering is emerging as a significant potential alternative or complementary solution, whereby tissue and organ failure is addressed by implanting natural, synthetic, orsemisynthetic tissueand organ mimics that are fully functional from the start or that grow into the required functionality. Initial efforts have focused on skin equivalents for treating burns, but an increasing number of tissue types are now being engineered, as well as biomaterials and scaffolds used as delivery systems. A variety of approaches are used to coax differentiated or undifferentiated cells, such as stem cells, into the desired cell type. Notable results includetissue-engineeredbone, blood vessels, liver, muscle, and even nerve conduits. As a result of the medical and market potential, there is significant academic and corporate interest in this technology.

Related Conferences

11th World Congress onBiotechnology and Biotech Industries Meet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 13thBiotechnology Congress, Nov 28-30, 2016, San Francisco, USA;Global Biotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA;Biomarker Summit2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccines Research & Development, July 7-8, Boston, USA;Pharmaceutical & BiotechPatent Litigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkers in Diagnostics, Oct 07-08, 2015 Berlin, Germany, DEU.

Track 12:Nano Biotechnology

Nano biotechnology, bio nanotechnology, and Nano biology are terms that refer to the intersection of nanotechnology and biology. Bio nanotechnology and Nano biotechnology serve as blanket terms for various related technologies. The most important objectives that are frequently found inNano biologyinvolve applying Nano tools to relevantmedical/biologicalproblems and refining these applications. Developing new tools, such as peptide Nano sheets, for medical and biological purposes is another primary objective in nanotechnology.

Related Conferences

8thWorldMedicalNanotechnologyCongress& Expo during June 9-11, Dallas, USA; 6thGlobal Experts Meeting and Expo onNanomaterialsand Nanotechnology, April 21-23, 2016 ,Dubai, UAE; 12thNanotechnologyProductsExpo, Nov 10-12, 2016 at Melbourne, Australia; 5thInternationalConference onNanotechand Expo, November 16-18, 2015 at San Antonio, USA; 11thInternational Conference and Expo onNano scienceandMolecular Nanotechnology, September 26-28 2016, London, UK; 18thInternational Conference onNanotechnologyand Biotechnology, February 4 - 5, 2016 in Melbourne, Australia; 16thInternational Conference onNanotechnology, August 22-25, 2016 in Sendai, Japan; International Conference onNano scienceand Nanotechnology, 7-11 Feb 2016 in Canberra, Australia; 18thInternational Conference onNano scienceand Nanotechnology, February 15 - 16, 2016 in Istanbul, Turkey; InternationalNanotechnologyConference& Expo, April 4-6, 2016 in Baltimore, USA.

Track 13:Bioinformatics and Biosensors

Bioinformatics is the application of computer technology to the management of biological information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied to gene-based drug discovery and development. The science of Bioinformatics, which is the melding of molecular biology with computer science, is essential to the use of genomic information in understanding human diseases and in the identification of newmolecular targetsfor drug discovery. This interesting field of science has many applications and research areas where it can be applied. It plays an essential role in today's plant science. As the amount of data grows exponentially, there is a parallel growth in the demand for tools and methods indata management, visualization, integration, analysis, modeling, and prediction.

Related conferences

11th World Congress onBiotechnology and Biotech IndustriesMeet, July 28-29, 2016, Berlin, Germany; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, Thailand; 11thEuro Biotechnology Congress, November 07-09,2016, Alicante Spain; 12thBiotechnology Congress, Nov 14-15, 2016, San Francisco, USA;BIO IPCC Conference, Cary, North Carolina, USA; World Congress onIndustrial Biotechnology, April 17-20, 2016, San Diego, CA; 6thBio based Chemicals: Commercialization & Partnering, November 16-17, 2015, San Francisco, CA, USA; The European Forum forIndustrial Biotechnology and Bio economy, 27-29 October 2015, Brussels, Belgium; 4thBiotechnology World Congress, February 15th-18th, 2016, Dubai, United Arab Emirates; International Conference on Advances inBioprocess Engineering and Technology, 20th to 22nd January 2016,Kolkata, India; GlobalBiotechnology Congress2016, May 11th - 14th 2016, Boston, MA, USA

Track 14:Biotechnology investments and Biotech grants

Every new business needs some startup capital, for research, product development and production, permits and licensing and other overhead costs, in addition to what is needed to pay your staff, if you have any. Biotechnology products arise from successfulbiotechcompanies. These companies are built by talented individuals in possession of a scientific breakthrough that is translated into a product or service idea, which is ultimately brought into commercialization. At the heart of this effort is the biotech entrepreneur, who forms the company with a vision they believe will benefit the lives and health of countless individuals. Entrepreneurs start biotechnology companies for various reasons, but creatingrevolutionary productsand tools that impact the lives of potentially millions of people is one of the fundamental reasons why all entrepreneurs start biotechnology companies.

10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok; 11thEuroBiotechnologyCongress, November 7-9, 2016 Alicante, Spain; 11th World Congress onBiotechnology and Biotech IndustriesMeet, July 28-29, 2016, Berlin, Germany; 13thBiotechnologyCongress, November 28-30, 2016 San Francisco, USA; 10thAsia Pacific Biotech CongressJuly 25-27, 2016, Bangkok, UAE;BioInternational Convention, June 6-9, 2016 | San Francisco, CA;BiotechJapan, May 11-13, 2016, Tokyo, Japan;NANO BIOEXPO 2016, Jan. 27 - 29, 2016, Tokyo, Japan;ArabLabExpo2016, March 20-23, Dubai; 14thInternational exhibition for laboratory technology,chemical analysis, biotechnology and diagnostics, 12-14 Apr 2016, Moscow, Russia

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Considering a Masters in Biotechnology Program or reviewing options for Masters Degrees in Biotechnology? A Masters in Biotechnology can openupexciting

Biotechnology is a challenging field that can involve a number of facets of both science and business or law. Many biotechnology master's degree programs focus on aspects of biology, cell biology, chemistry, or biological or chemical engineering. In general, biotechnology degrees involve research whether they are at a Masters or PhD level.

Scientific understanding is rapidly evolving, particularly in areas of cellular and molecular systems. Biotechnology master's students can therefore enjoy rich study opportunities particularly in fields such as genetic engineering, the Human Genome project, the production of new medicinal products, and research into the relationship between genetic malfunction and the origin of disease. These are just a few of the many areas that biotechnology students have the opportunity to explore today.

Another focus of biotechnology masters programs may be to equip students with the combination of science and business knowledge they need to help produce products and move them toward production. Today's complex business environment and government regulations require many steps and people with the ability to both understand and help produce new scientific technologies as well as get them approved and be able to market them.

Master degrees in biotechnology might prepare students to pursue careers in a variety of industries. While many students go on to further research or academic positions, there may also be some demand for biotechnologists outside of academia, both in the government and private sectors. Biotechnologists might pursue careers in anything from research to applied science and manufacturing. Those with specializations in business aspects of biotechnology may be qualified to pursue management positions within organizations attempting to produce and market new biotechnology.

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Masters in Biotechnology Programs and ... - Masters PhD Degrees

Drosophila melanogaster is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting with Charles W. Woodworth's proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in studies of genetics, physiology, microbial pathogenesis, and life history evolution. It is typically used because it is an animal species that is easy to care for, has four pairs of chromosomes, breeds quickly, and lays many eggs.[2]D. melanogaster is a common pest in homes, restaurants, and other occupied places where food is served.[3]

Flies belonging to the family Tephritidae are also called "fruit flies". This can cause confusion, especially in Australia and South Africa, where the Mediterranean fruit fly Ceratitis capitata is an economic pest.

Wildtype fruit flies are yellow-brown, with brick-red eyes and transverse black rings across the abdomen. They exhibit sexual dimorphism: females are about 2.5 millimeters (0.098in) long; males are slightly smaller with darker backs. Males are easily distinguished from females based on colour differences, with a distinct black patch at the abdomen, less noticeable in recently emerged flies (see fig.), and the sexcombs (a row of dark bristles on the tarsus of the first leg). Furthermore, males have a cluster of spiky hairs (claspers) surrounding the reproducing parts used to attach to the female during mating. There are extensive images at FlyBase.[4]

Egg of D. melanogaster

The D. melanogaster lifespan is about 30 days at 29C (84F).

The developmental period for D. melanogaster varies with temperature, as with many ectothermic species. The shortest development time (egg to adult), 7 days, is achieved at 28C (82F).[5][6] Development times increase at higher temperatures (11 days at 30C or 86F) due to heat stress. Under ideal conditions, the development time at 25C (77F) is 8.5 days,[5][6][7] at 18C (64F) it takes 19 days[5][6] and at 12C (54F) it takes over 50 days.[5][6] Under crowded conditions, development time increases,[8] while the emerging flies are smaller.[8][9] Females lay some 400 eggs (embryos), about five at a time, into rotting fruit or other suitable material such as decaying mushrooms and sap fluxes. The eggs, which are about 0.5mm long, hatch after 1215 hours (at 25C or 77F).[5][6] The resulting larvae grow for about 4 days (at 25C) while molting twice (into second- and third-instar larvae), at about 24 and 48 h after hatching.[5][6] During this time, they feed on the microorganisms that decompose the fruit, as well as on the sugar of the fruit itself. The mother puts feces on the egg sacs to establish the same microbial composition in the larvae's guts which has worked positively for herself.[10] Then the larvae encapsulate in the puparium and undergo a four-day-long metamorphosis (at 25C), after which the adults eclose (emerge).[5][6]

Females become receptive to courting males at about 812 hours after emergence.[11] Specific neuron groups in females have been found to affect copulation behavior and mate choice. One such group in the abdominal nerve cord allows the female fly to pause her body movements to copulate.[12] Activation of these neurons induces the female to cease movement and orient herself towards the male to allow for mounting. If the group is inactivated, the female remains in motion and does not copulate. Various chemical signals such as male pheromones often are able to activate the group.[12]

The female fruit fly prefers a shorter duration when it comes to sex. Males, on the other hand, prefer it to last longer.[13] Males perform a sequence of five behavioral patterns to court females. First, males orient themselves while playing a courtship song by horizontally extending and vibrating their wings. Soon after, the male positions itself at the rear of the female's abdomen in a low posture to tap and lick the female genitalia. Finally, the male curls its abdomen and attempts copulation. Females can reject males by moving away, kicking, and extruding their ovipositor.[14] Copulation lasts around 1520 minutes,[15] during which males transfer a few hundred, very long (1.76mm) sperm cells in seminal fluid to the female.[16] Females store the sperm in a tubular receptacle and in two mushroom-shaped spermathecae; sperm from multiple matings compete for fertilization. A last male precedence is believed to exist in which the last male to mate with a female sires about 80% of her offspring. This precedence was found to occur through both displacement and incapacitation.[17] The displacement is attributed to sperm handling by the female fly as multiple matings are conducted and is most significant during the first 12 days after copulation. Displacement from the seminal receptacle is more significant than displacement from the spermathecae.[17] Incapacitation of first male sperm by second male sperm becomes significant 27 days after copulation. The seminal fluid of the second male is believed to be responsible for this incapacitation mechanism (without removal of first male sperm) which takes effect before fertilization occurs.[17] The delay in effectiveness of the incapacitation mechanism is believed to be a protective mechanism that prevents a male fly from incapacitating its own sperm should it mate with the same female fly repetitively. Sensory neurons in the uterus of female D. melanogaster respond to a male protein, sex peptide, which is found in sperm.[12] This protein makes the female reluctant to copulate for about 10 days after insemination. The signal pathway leading to this change in behavior has been determined. The signal is sent to a brain region that is a homolog of the hypothalamus and the hypothalamus then controls sexual behavior and desire[12]

D. melanogaster is often used for life extension studies, such as to identify genes purported to increase lifespan when mutated.[18]

D. melanogaster females exhibit mate choice copying. When virgin females are shown other females copulating with a certain type of male, they tend to copulate more with this type of male afterwards than naive females (which have not observed the copulation of others). This behavior is sensitive to environmental conditions, and females copy less in bad weather conditions.[19]

D. melanogaster males exhibit a strong reproductive learning curve. That is, with sexual experience, these flies tend to modify their future mating behavior in multiple ways. These changes include increased selectivity for courting only intraspecifically, as well as decreased courtship times.

Sexually nave D. melanogaster males are known to spend significant time courting interspecifically, such as with D. simulans flies. Nave D. melanogaster will also attempt to court females that are not yet sexually mature, and other males. D. melanogaster males show little to no preference for D. melanogaster females over females of other species or even other male flies. However, after D. simulans or other flies incapable of copulation have rejected the males advances, D. melanogaster males are much less likely to spend time courting nonspecifically in the future. This apparent learned behavior modification seems to be evolutionarily significant, as it allows the males to avoid investing energy into futile sexual encounters.[20]

In addition, males with previous sexual experience will modify their courtship dance when attempting to mate with new females the experienced males spend less time courting and therefore have lower mating latencies, meaning that they are able to reproduce more quickly. This decreased mating latency leads to a greater mating efficiency for experienced males over nave males.[21] This modification also appears to have obvious evolutionary advantages, as increased mating efficiency is extremely important in the eyes of natural selection.

Both male and female D. melanogaster act polygamously (having multiple sexual partners at the same time).[22] In both males and females, polygamy results in a decrease in evening activity compared to virgin flies, more so in males than females.[22] Evening activity consists of the activities that the flies participate in other than mating and finding partners, such as finding food.[23] The reproductive success of males and females varies, due to the fact that a female only needs to mate once to reach maximum fertility.[23] Mating with multiple partners provides no advantage over mating with one partner, and therefore females exhibit no difference in evening activity between polygamous and monogamous individuals.[23] For males, however, mating with multiple partners increases their reproductive success by increasing the genetic diversity of their offspring.[23] This benefit of genetic diversity is an evolutionary advantage because it increases the chance that some of the offspring will have traits that increase their fitness in their environment.

The difference in evening activity between polygamous and monogamous male flies can be explained with courtship. For polygamous flies, their reproductive success increases by having offspring with multiple partners, and therefore they spend more time and energy on courting multiple females.[23] On the other hand, monogamous flies only court one female, and expend less energy doing so.[23] While it requires more energy for male flies to court multiple females, the overall reproductive benefits it produces has kept polygamy as the preferred sexual choice.[23]

It has been shown that the mechanism that affects courtship behavior in Drosophila is controlled by the oscillator neurons DN1s and LNDs.[24] Oscillation of the DN1 neurons was found to be effected by socio-sexual interactions, and is connected to mating-related decrease of evening activity.[24]

D. melanogaster was among the first organisms used for genetic analysis, and today it is one of the most widely used and genetically best-known of all eukaryotic organisms. All organisms use common genetic systems; therefore, comprehending processes such as transcription and replication in fruit flies helps in understanding these processes in other eukaryotes, including humans.[25]

Thomas Hunt Morgan began using fruit flies in experimental studies of heredity at Columbia University in 1910 in a laboratory known as the Fly Room. The Fly Room was cramped with eight desks, each occupied by students and their experiments. They started off experiments using milk bottles to rear the fruit flies and handheld lenses for observing their traits. The lenses were later replaced by microscopes, which enhanced their observations. Morgan and his students eventually elucidated many basic principles of heredity, including sex-linked inheritance, epistasis, multiple alleles, and gene mapping.[25]

D. melanogaster is one of the most studied organisms in biological research, particularly in genetics and developmental biology. The several reasons include:

Genetic markers are commonly used in Drosophila research, for example within balancer chromosomes or P-element inserts, and most phenotypes are easily identifiable either with the naked eye or under a microscope. In the list of example common markers below, the allele symbol is followed by the name of the gene affected and a description of its phenotype. (Note: Recessive alleles are in lower case, while dominant alleles are capitalised.)

Drosophila genes are traditionally named after the phenotype they cause when mutated. For example, the absence of a particular gene in Drosophila will result in a mutant embryo that does not develop a heart. Scientists have thus called this gene tinman, named after the Oz character of the same name.[27] This system of nomenclature results in a wider range of gene names than in other organisms.

The genome of D. melanogaster (sequenced in 2000, and curated at the FlyBase database[26]) contains four pairs of chromosomes: an X/Y pair, and three autosomes labeled 2, 3, and 4. The fourth chromosome is so tiny, it is often ignored, aside from its important eyeless gene. The D. melanogaster sequenced genome of 139.5 million base pairs has been annotated[28] and contains around 15,682 genes according to Ensemble release 73. More than 60% of the genome appears to be functional non-protein-coding DNA[29] involved in gene expression control. Determination of sex in Drosophila occurs by the X:A ratio of X chromosomes to autosomes, not because of the presence of a Y chromosome as in human sex determination. Although the Y chromosome is entirely heterochromatic, it contains at least 16 genes, many of which are thought to have male-related functions.[30]

A March 2000 study by National Human Genome Research Institute comparing the fruit fly and human genome estimated that about 60% of genes are conserved between the two species.[31] About 75% of known human disease genes have a recognizable match in the genome of fruit flies,[32] and 50% of fly protein sequences have mammalian homologs. An online database called Homophila is available to search for human disease gene homologues in flies and vice versa.[33]Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying aging and oxidative stress, immunity, diabetes, and cancer, as well as drug abuse.

Embryogenesis in Drosophila has been extensively studied, as its small size, short generation time, and large brood size makes it ideal for genetic studies. It is also unique among model organisms in that cleavage occurs in a syncytium.

During oogenesis, cytoplasmic bridges called "ring canals" connect the forming oocyte to nurse cells. Nutrients and developmental control molecules move from the nurse cells into the oocyte. In the figure to the left, the forming oocyte can be seen to be covered by follicular support cells.

After fertilization of the oocyte, the early embryo (or syncytial embryo) undergoes rapid DNA replication and 13 nuclear divisions until about 5000 to 6000 nuclei accumulate in the unseparated cytoplasm of the embryo. By the end of the eighth division, most nuclei have migrated to the surface, surrounding the yolk sac (leaving behind only a few nuclei, which will become the yolk nuclei). After the 10th division, the pole cells form at the posterior end of the embryo, segregating the germ line from the syncytium. Finally, after the 13th division, cell membranes slowly invaginate, dividing the syncytium into individual somatic cells. Once this process is completed, gastrulation starts.[34]

Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in division of the DNA. To get around this problem, the nuclei that have made a mistake detach from their centrosomes and fall into the centre of the embryo (yolk sac), which will not form part of the fly.

The gene network (transcriptional and protein interactions) governing the early development of the fruit fly embryo is one of the best understood gene networks to date, especially the patterning along the anteroposterior (AP) and dorsoventral (DV) axes (See under morphogenesis).[34]

The embryo undergoes well-characterized morphogenetic movements during gastrulation and early development, including germ-band extension, formation of several furrows, ventral invagination of the mesoderm, and posterior and anterior invagination of endoderm (gut), as well as extensive body segmentation until finally hatching from the surrounding cuticle into a first-instar larva.

During larval development, tissues known as imaginal discs grow inside the larva. Imaginal discs develop to form most structures of the adult body, such as the head, legs, wings, thorax, and genitalia. Cells of the imaginal disks are set aside during embryogenesis and continue to grow and divide during the larval stagesunlike most other cells of the larva, which have differentiated to perform specialized functions and grow without further cell division. At metamorphosis, the larva forms a pupa, inside which the larval tissues are reabsorbed and the imaginal tissues undergo extensive morphogenetic movements to form adult structures.

Drosophila flies have both X and Y chromosomes, as well as autosomes. Unlike humans, the Y chromosome does not confer maleness; rather, it encodes genes necessary for making sperm. Sex is instead determined by the ratio of X chromosomes to autosomes. Furthermore, each cell "decides" whether to be male or female independently of the rest of the organism, resulting in the occasional occurrence of gynandromorphs.

Three major genes are involved in determination of Drosophila sex. These are sex-lethal, sisterless, and deadpan. Deadpan is an autosomal gene which inhibits sex-lethal, while sisterless is carried on the X chromosome and inhibits the action of deadpan. An AAX cell has twice as much deadpan as sisterless, so sex-lethal will be inhibited, creating a male. However, an AAXX cell will produce enough sisterless to inhibit the action of deadpan, allowing the sex-lethal gene to be transcribed to create a female.

Later, control by deadpan and sisterless disappears and what becomes important is the form of the sex-lethal gene. A secondary promoter causes transcription in both males and females. Analysis of the cDNA has shown that different forms are expressed in males and females. Sex-lethal has been shown to affect the splicing of its own mRNA. In males, the third exon is included which encodes a stop codon, causing a truncated form to be produced. In the female version, the presence of sex-lethal causes this exon to be missed out; the other seven amino acids are produced as a full peptide chain, again giving a difference between males and females.[35]

Presence or absence of functional sex-lethal proteins now go on to affect the transcription of another protein known as doublesex. In the absence of sex-lethal, doublesex will have the fourth exon removed and be translated up to and including exon 6 (DSX-M[ale]), while in its presence the fourth exon which encodes a stop codon will produce a truncated version of the protein (DSX-F[emale]). DSX-F causes transcription of Yolk proteins 1 and 2 in somatic cells, which will be pumped into the oocyte on its production.

Unlike mammals, Drosophila flies only have innate immunity and lack an adaptive immune response. The D. melanogaster immune system can be divided into two responses: humoral and cell-mediated. The former is a systemic response mediated through the Toll and imd pathways, which are parallel systems for detecting microbes. The Toll pathway in Drosophila is known as the homologue of Toll-like pathways in mammals. Spatzle, a known ligand for the Toll pathway in flies, is produced in response to Gram-positive bacteria, parasites, and fungal infection. Upon infection, pro-Spatzle will be cleaved by protease SPE (Spatzle processing enzyme) to become active Spatzle, which then binds to the Toll receptor located on the cell surface (Fat body, hemocytes) and dimerise for activation of downstream NF-B signaling pathways. The imd pathway, though, is triggered by Gram-negative bacteria through soluble and surface receptors (PGRP-LE and LC, respectively). D. melanogaster has a "fat body", which is thought to be homologous to the human liver. It is the primary secretory organ and produces antimicrobial peptides. These peptides are secreted into the hemolymph and bind infectious bacteria, killing them by forming pores in their cell walls. Years ago[when?] many drug companies wanted to purify these peptides and use them as antibiotics. Other than the fat body, hemocytes, the blood cells in Drosophila, are known as the homologue of mammalian monocyte/macrophages, possessing a significant role in immune responses. It is known from the literature that in response to immune challenge, hemocytes are able to secrete cytokines, for example Spatzle, to activate downstream signaling pathways in the fat body. However, the mechanism still remains unclear.

In 1971, Ron Konopka and Seymour Benzer published "Clock mutants of Drosophila melanogaster", a paper describing the first mutations that affected an animal's behavior. Wild-type flies show an activity rhythm with a frequency of about a day (24 hours). They found mutants with faster and slower rhythms, as well as broken rhythmsflies that move and rest in random spurts. Work over the following 30 years has shown that these mutations (and others like them) affect a group of genes and their products that comprise a biochemical or biological clock. This clock is found in a wide range of fly cells, but the clock-bearing cells that control activity are several dozen neurons in the fly's central brain.

Since then, Benzer and others have used behavioral screens to isolate genes involved in vision, olfaction, audition, learning/memory, courtship, pain, and other processes, such as longevity.

The first learning and memory mutants (dunce, rutabaga, etc.) were isolated by William "Chip" Quinn while in Benzer's lab, and were eventually shown to encode components of an intracellular signaling pathway involving cyclic AMP, protein kinase A, and a transcription factor known as CREB. These molecules were shown to be also involved in synaptic plasticity in Aplysia and mammals.[citation needed]

Male flies sing to the females during courtship using their wings to generate sound, and some of the genetics of sexual behavior have been characterized. In particular, the fruitless gene has several different splice forms, and male flies expressing female splice forms have female-like behavior and vice versa. The TRP channels nompC, nanchung, and inactive are expressed in sound-sensitive Johnston's organ neurons and participate in the transduction of sound.[36][37]

Furthermore, Drosophila has been used in neuropharmacological research, including studies of cocaine and alcohol consumption. Models for Parkinson's disease also exist for flies.[38]

Stereo images of the fly eye

The compound eye of the fruit fly contains 760 unit eyes or ommatidia, and are one of the most advanced among insects. Each ommatidium contains eight photoreceptor cells (R1-8), support cells, pigment cells, and a cornea. Wild-type flies have reddish pigment cells, which serve to absorb excess blue light so the fly is not blinded by ambient light.

Each photoreceptor cell consists of two main sections, the cell body and the rhabdomere. The cell body contains the nucleus, while the 100-m-long rhabdomere is made up of toothbrush-like stacks of membrane called microvilli. Each microvillus is 12 m in length and about 60 nm in diameter.[39] The membrane of the rhabdomere is packed with about 100 million rhodopsin molecules, the visual protein that absorbs light. The rest of the visual proteins are also tightly packed into the microvillar space, leaving little room for cytoplasm.

The photoreceptors in Drosophila express a variety of rhodopsin isoforms. The R1-R6 photoreceptor cells express rhodopsin1 (Rh1), which absorbs blue light (480nm). The R7 and R8 cells express a combination of either Rh3 or Rh4, which absorb UV light (345nm and 375nm), and Rh5 or Rh6, which absorb blue (437nm) and green (508nm) light, respectively. Each rhodopsin molecule consists of an opsin protein covalently linked to a carotenoid chromophore, 11-cis-3-hydroxyretinal.[40]

As in vertebrate vision, visual transduction in invertebrates occurs via a G protein-coupled pathway. However, in vertebrates, the G protein is transducin, while the G protein in invertebrates is Gq (dgq in Drosophila). When rhodopsin (Rh) absorbs a photon of light its chromophore, 11-cis-3-hydroxyretinal, is isomerized to all-trans-3-hydroxyretinal. Rh undergoes a conformational change into its active form, metarhodopsin. Metarhodopsin activates Gq, which in turn activates a phospholipase C (PLC) known as NorpA.[41]

PLC hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP2), a phospholipid found in the cell membrane, into soluble inositol triphosphate (IP3) and diacylglycerol (DAG), which stays in the cell membrane. DAG or a derivative of DAG causes a calcium-selective ion channel known as transient receptor potential (TRP) to open and calcium and sodium flows into the cell. IP3 is thought to bind to IP3 receptors in the subrhabdomeric cisternae, an extension of the endoplasmic reticulum, and cause release of calcium, but this process does not seem to be essential for normal vision.[41]

Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins interact with other proteins and have been shown to be necessary for shut off of the light response. In addition, proteins called arrestins bind metarhodopsin and prevent it from activating more Gq. A sodium-calcium exchanger known as CalX pumps the calcium out of the cell. It uses the inward sodium gradient to export calcium at a stoichiometry of 3 Na+/ 1 Ca++.[42]

TRP, InaC, and PLC form a signaling complex by binding a scaffolding protein called InaD. InaD contains five binding domains called PDZ domain proteins, which specifically bind the C termini of target proteins. Disruption of the complex by mutations in either the PDZ domains or the target proteins reduces the efficiency of signaling. For example, disruption of the interaction between InaC, the protein kinase C, and InaD results in a delay in inactivation of the light response.

Unlike vertebrate metarhodopsin, invertebrate metarhodopsin can be converted back into rhodopsin by absorbing a photon of orange light (580nm).

About two-thirds of the Drosophila brain is dedicated to visual processing.[43] Although the spatial resolution of their vision is significantly worse than that of humans, their temporal resolution is around 10 times better.

The wings of a fly are capable of beating up to 220 times per second.[citation needed] Flies fly via straight sequences of movement interspersed by rapid turns called saccades.[44] During these turns, a fly is able to rotate 90 in less than 50 milliseconds.[44]

Characteristics of Drosophila flight may be dominated by the viscosity of the air, rather than the inertia of the fly body, but the opposite case with inertia as the dominant force may occur.[44] However, subsequent work showed that while the viscous effects on the insect body during flight may be negligible, the aerodynamic forces on the wings themselves actually cause fruit flies' turns to be damped viscously.[45]

Drosophila is commonly considered a pest due to its tendency to infest habitations and establishments where fruit is found; the flies may collect in homes, restaurants, stores, and other locations.[3] Removal of an infestation can be difficult, as larvae may continue to hatch in nearby fruit even as the adult population is eliminated.

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Executive Summary

This executive summary reviews the topics covered in this PDQ summary on the genetics of skin cancer, with hyperlinks to detailed sections below that describe the evidence on each topic.

More than 100 types of tumors are clinically apparent on the skin; many are known to have familial and/or inherited components, either in isolation or as part of a syndrome with other features. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which are known collectively as nonmelanoma skin cancer, are two of the most common malignancies in the United States and are often caused by sun exposure, although several hereditary syndromes and genes are also associated with an increased risk of developing these cancers. Melanoma is less common than nonmelanoma skin cancer, but 5% to 10% of all melanomas arise in multiple-case families and may be inherited in an autosomal dominant fashion.

Several genes and hereditary syndromes are associated with the development of skin cancer. Basal cell nevus syndrome (BCNS, caused by pathogenic variants in PTCH1 and PTCH2) is associated with an increased risk of BCC, while syndromes such as xeroderma pigmentosum (XP), oculocutaneous albinism, epidermolysis bullosa, and Fanconi anemia are associated with an increased risk of SCC. The major tumor suppressor gene associated with melanoma is CDKN2A; pathogenic variants in CDKN2A have been estimated to account for 35% to 40% of all familial melanomas. Pathogenic variants in many other genes, including CDK4, CDK6, BAP1, and BRCA2, have also been found to be associated with melanoma.

Genome-wide searches are showing promise in identifying common, low-penetrance susceptibility alleles for many complex diseases, including melanoma, but the clinical utility of these findings remains uncertain.

Risk-reducing strategies for individuals with an increased hereditary predisposition to skin cancer are similar to recommendations for the general population, and include sun avoidance, use of sunscreen, use of sun-protective clothing, and avoidance of tanning beds. Chemopreventive agents such as isotretinoin and acitretin have been studied for the treatment of BCCs in patients with BCNS and XP and are associated with a significant decrease in the number of tumors per year. Vismodegib has also shown promise in reducing the per-patient annual rate of new BCCs requiring surgery among patients with BCNS. Isotretinoin has also been shown to reduce SCC incidence among patients with XP.

Treatment of hereditary skin cancers is similar to the treatment of sporadic skin cancers. One study in an XP population found therapeutic use of 5-fluorouracil to be efficacious, particularly in the treatment of extensive lesions. In addition to its role as a therapeutic and potential chemopreventive agent, vismodegib is also being studied for potential palliative effects for keratocystic odontogenic tumors in patients with BCNS.

Most of the psychosocial literature about hereditary skin cancers has focused on patients with familial melanoma. In individuals at risk of familial melanoma, psychosocial factors influence decisions about genetic testing for inherited cancer risk and risk-management strategies. Interest in genetic testing for pathogenic variants in CDKN2A is generally high. Perceived benefits among individuals with a strong family history of melanoma include information about the risk of melanoma for themselves and their children and increased motivation for sun-protective behavior. A number of studies have examined risk-reducing and early-detection behaviors in individuals with a family history of melanoma. Overall, these studies indicate inconsistent adoption and maintenance of these behaviors. Intervention studies have targeted knowledge about melanoma, sun protection, and screening behaviors in family members of melanoma patients, with mixed results. Research is ongoing to better understand and address psychosocial and behavioral issues in high-risk families.

[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

[Note: A concerted effort is being made within the genetics community to shift terminology used to describe genetic variation. The shift is to use the term variant rather than the term mutation to describe a difference that exists between the person or group being studied and the reference sequence. Variants can then be further classified as benign (harmless), likely benign, of uncertain significance, likely pathogenic, or pathogenic (disease causing). Throughout this summary, we will use the term pathogenic variant to describe a disease-causing mutation. Refer to the Cancer Genetics Overview summary for more information about variant classification.]

[Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

The genetics of skin cancer is an extremely broad topic. There are more than 100 types of tumors that are clinically apparent on the skin; many of these are known to have familial components, either in isolation or as part of a syndrome with other features. This is, in part, because the skin itself is a complex organ made up of multiple cell types. Furthermore, many of these cell types can undergo malignant transformation at various points in their differentiation, leading to tumors with distinct histology and dramatically different biological behaviors, such as squamous cell carcinoma (SCC) and basal cell cancer (BCC). These have been called nonmelanoma skin cancers or keratinocyte cancers.

Figure 1 is a simple diagram of normal skin structure. It also indicates the major cell types that are normally found in each compartment. Broadly speaking, there are two large compartmentsthe avascular epidermis and the vascular dermiswith many cell types distributed in a largely acellular matrix.[1]

Figure 1. Schematic representation of normal skin. The relatively avascular epidermis houses basal cell keratinocytes and squamous epithelial keratinocytes, the source cells for BCC and SCC, respectively. Melanocytes are also present in normal skin and serve as the source cell for melanoma. The separation between epidermis and dermis occurs at the basement membrane zone, located just inferior to the basal cell keratinocytes.

The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations. The bottom layer is formed of basal keratinocytes abutting the basement membrane. The basement membrane is formed from products of keratinocytes and dermal fibroblasts, such as collagen and laminin, and is an important anatomical and functional structure. Basal keratinocytes lose contact with the basement membrane as they divide. As basal keratinocytes migrate toward the skin surface, they progressively differentiate to form the spinous cell layer; the granular cell layer; and the keratinized outer layer, or stratum corneum.

The true cytologic origin of BCC remains in question. BCC and basal cell keratinocytes share many histologic similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC.[2] This is suggested by the fact that BCCs occur predominantly on hair-bearing skin. BCCs rarely metastasize but can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name "rodent ulcer."[3]

Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source. Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3]

Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can undergo malignant transformation into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age. Langerhans cells, or dendritic cells, are another cell type in the epidermis and have a primary function of antigen presentation. These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[5]

The dermis is largely composed of an extracellular matrix. Prominent cell types in this compartment are fibroblasts, endothelial cells, and transient immune system cells. When transformed, fibroblasts form fibrosarcomas and endothelial cells form angiosarcomas, Kaposi sarcoma, and other vascular tumors. There are a number of immune cell types that move in and out of the skin to blood vessels and lymphatics; these include mast cells, lymphocytes, mononuclear cells, histiocytes, and granulocytes. These cells can increase in number in inflammatory diseases and can form tumors within the skin. For example, urticaria pigmentosa is a condition that arises from mast cells and is occasionally associated with mast cell leukemia; cutaneous T-cell lymphoma is often confined to the skin throughout its course. Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[6]

Epidermal appendages are also found in the dermal compartment. These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles. These structures are generally formed in the first and second trimesters of fetal development. These can form a large variety of benign or malignant tumors with diverse biological behaviors. Several of these tumors are associated with familial syndromes. Overall, there are dozens of different histological subtypes of these tumors associated with individual components of the adnexal structures.[7]

Finally, the subcutis is a layer that extends below the dermis with varying depth, depending on the anatomic location. This deeper boundary can include muscle, fascia, bone, or cartilage. The subcutis can be affected by inflammatory conditions such as panniculitis and malignancies such as liposarcoma.[8]

These compartments give rise to their own malignancies but are also the region of immediate adjacent spread of localized skin cancers from other compartments. The boundaries of each skin compartment are used to define the staging of skin cancers. For example, an in situ melanoma is confined to the epidermis. Once the cancer crosses the basement membrane into the dermis, it is invasive. Internal malignancies also commonly metastasize to the skin. The dermis and subcutis are the most common locations, but the epidermis can also be involved in conditions such as Pagetoid breast cancer.

The skin has a wide variety of functions. First, the skin is an important barrier preventing extensive water and temperature loss and providing protection against minor abrasions. These functions can be aberrantly regulated in cancer. For example, in the erythroderma (reddening of the skin) associated with advanced cutaneous T-cell lymphoma, alterations in the regulations of body temperature can result in profound heat loss. Second, the skin has important adaptive and innate immunity functions. In adaptive immunity, antigen-presenting cells engender T-cell responses consisting of increased levels of TH1, TH2, or TH17 cells.[9] In innate immunity, the immune system produces numerous peptides with antibacterial and antifungal capacity. Consequently, even small breaks in the skin can lead to infection. The skin-associated lymphoid tissue is one of the largest arms of the immune system. It may also be important in immune surveillance against cancer. Immunosuppression, which occurs during organ transplant, is a significant risk factor for skin cancer. The skin is significant for communication through facial expression and hand movements. Unfortunately, areas of specialized function, such as the area around the eyes and ears, are common places for cancer to occur. Even small cancers in these areas can lead to reconstructive challenges and have significant cosmetic and social ramifications.[1]

While the appearance of any one skin cancer can vary, there are general physical presentations that can be used in screening. BCCs most commonly have a pearly rim or can appear somewhat eczematous (see Figure 2 and Figure 3). They often ulcerate (see Figure 2). SCCs frequently have a thick keratin top layer (see Figure 4). Both BCCs and SCCs are associated with a history of sun-damaged skin. Melanomas are characterized by asymmetry, border irregularity, color variation, a diameter of more than 6 mm, and evolution (ABCDE criteria). (Refer to What Does Melanoma Look Like? on NCI's website for more information about the ABCDE criteria.) Photographs representing typical clinical presentations of these cancers are shown below.

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Figure 2. Ulcerated basal cell carcinoma (left panel) and ulcerated basal cell carcinoma with characteristic pearly rim (right panel).

Figure 3. Superficial basal cell carcinoma (left panel) and nodular basal cell carcinoma (right panel).

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Figure 4. Squamous cell carcinoma on the face with thick keratin top layer (left panel) and squamous cell carcinoma on the leg (right panel).

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Figure 5. Melanomas with characteristic asymmetry, border irregularity, color variation, and large diameter.

Basal cell carcinoma (BCC) is the most common malignancy in people of European descent, with an associated lifetime risk of 30%.[1] While exposure to ultraviolet (UV) radiation is the risk factor most closely linked to the development of BCC, other environmental factors (such as ionizing radiation, chronic arsenic ingestion, and immunosuppression) and genetic factors (such as family history, skin type, and genetic syndromes) also potentially contribute to carcinogenesis. In contrast to melanoma, metastatic spread of BCC is very rare and typically arises from large tumors that have evaded medical treatment for extended periods of time. BCCs can invade tissue locally or regionally, sometimes following along nerves. A tendency for superficial necrosis has resulted in the name "rodent ulcer." With early detection, the prognosis for BCC is excellent.

This section focuses on risk factors in individuals at increased hereditary risk of developing BCC. (Refer to the PDQ summary on Skin Cancer Prevention for information about risk factors for BCC in the general population.)

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types. There are different patterns of sun exposure associated with each major type of skin cancer (BCC, squamous cell carcinoma [SCC], and melanoma). (Refer to the PDQ summary on Skin Cancer Prevention for more information about sun exposure as a risk factor for skin cancer in the general population.)

The high-risk phenotype consists of individuals with the following physical characteristics:

Specifically, people with more highly pigmented skin demonstrate lower incidence of BCC than do people with lighter pigmented skin. Individuals with Fitzpatrick Type I or II skin were shown to have a twofold increased risk of BCC in a small case-control study.[2] (Refer to the Pigmentary characteristics section in the Melanoma section of this summary for a more detailed discussion of skin phenotypes based upon pigmentation.) Blond or red hair color was associated with increased risk of BCC in two large cohorts: the Nurses Health Study and the Health Professionals Follow-Up Study.[3] In women from the Nurses Health Study, there was an increased risk of BCC in women with red hair relative to those with light brown hair (adjusted relative risk [RR], 1.30; 95% confidence interval [CI], 1.201.40). In men from the Health Professionals Follow-Up Study, the risk of BCC associated with red hair was lower (RR, 1.17; 95% CI, 1.021.34) and was not significant after adjustment for melanoma family history and sunburn history.[3] Risk associated with blond hair was also increased for both men and women (RR, pooled analysis, 1.09; 95% CI, 1.021.18), and dark brown hair was protective against BCC (RR, pooled analysis, 0.89; 95% CI 0.870.92).

Individuals with BCCs and/or SCCs report a higher frequency of these cancers in their family members than do controls. The importance of this finding is unclear. Apart from defined genetic disorders with an increased risk of BCC, a positive family history of any skin cancer is a strong predictor of the development of BCC. Data from the Nurses Health Study and the Health Professionals Follow-Up Study indicate that the family history of melanoma in a first-degree relative (FDR) is associated with an increased risk of BCC in both men and women (RR, 1.31; 95% CI, 1.251.37; P <.0001).[3] A study of 376 early-onset BCC cases and 383 controls found that a family history of any type of skin cancer increased the risk of early-onset BCC (odds ratio [OR], 2.49; 95% CI, 1.803.45). This risk increased when an FDR was diagnosed with skin cancer before age 50 years (OR, 4.79; 95% CI, 2.907.90). Individuals who had a family history of both melanoma and nonmelanoma skin cancer (NMSC) had the highest risk (OR, 3.65; 95% CI, 1.797.47).[4]

A study on the heritability of cancer among 80,309 monozygotic and 123,382 dizygotic twins showed that NMSCs have a heritability of 43% (95% CI, 26%59%), suggesting that almost half of the risk of NMSC is caused by inherited factors.[5] Additionally, the cumulative risk of NMSC was 1.9-fold higher for monozygotic than for dizygotic twins (95% CI, 1.82.0).[5]

A personal history of BCC or SCC is strongly associated with subsequent BCC or SCC. There is an approximate 20% increased risk of a subsequent lesion within the first year after a skin cancer has been diagnosed. The mean age of occurrence for these NMSCs is the mid-60s.[6-11] In addition, several studies have found that individuals with a history of skin cancer have an increased risk of a subsequent diagnosis of a noncutaneous cancer;[12-15] however, other studies have contradicted this finding.[16-19] In the absence of other risk factors or evidence of a defined cancer susceptibility syndrome, as discussed below, skin cancer patients are encouraged to follow screening recommendations for the general population for sites other than the skin.

Pathogenic variants in the gene coding for the transmembrane receptor protein PTCH1, or PTCH, are associated with basal cell nevus syndrome (BCNS) and sporadic cutaneous BCCs. (Refer to the BCNS section of this summary for more information.) PTCH1, the human homolog of the Drosophila segment polarity gene patched (ptc), is an integral component of the hedgehog signaling pathway, which serves many developmental (appendage development, embryonic segmentation, neural tube differentiation) and regulatory (maintenance of stem cells) roles.

In the resting state, the transmembrane receptor protein PTCH1 acts catalytically to suppress the seven-transmembrane protein Smoothened (Smo), preventing further downstream signal transduction.[20] Binding of the hedgehog ligand to PTCH1 releases inhibition of Smo, with resultant activation of transcription factors (GLI1, GLI2), cell proliferation genes (cyclin D, cyclin E, myc), and regulators of angiogenesis.[21,22] Thus, the balance of PTCH1 (inhibition) and Smo (activation) manages the essential regulatory downstream hedgehog signal transduction pathway. Loss-of-function pathogenic variants of PTCH1 or gain-of-function variants of Smo tip this balance toward activation, a key event in potential neoplastic transformation.

Demonstration of allelic loss on chromosome 9q22 in both sporadic and familial BCCs suggested the potential presence of an associated tumor suppressor gene.[23,24] Further investigation identified a pathogenic variant in PTCH1 that localized to the area of allelic loss.[25] Up to 30% of sporadic BCCs demonstrate PTCH1 pathogenic variants.[26] In addition to BCC, medulloblastoma and rhabdomyosarcoma, along with other tumors, have been associated with PTCH1 pathogenic variants. All three malignancies are associated with BCNS, and most people with clinical features of BCNS demonstrate PTCH1 pathogenic variants, predominantly truncation in type.[27]

Truncating pathogenic variants in PTCH2, a homolog of PTCH1 mapping to chromosome 1p32.1-32.3, have been demonstrated in both BCC and medulloblastoma.[28,29] PTCH2 displays 57% homology to PTCH1.[30] While the exact role of PTCH2 remains unclear, there is evidence to support its involvement in the hedgehog signaling pathway.[28,31]

Pathogenic variants in the BAP1 gene are associated with an increased risk of a variety of cancers, including cutaneous melanoma and uveal melanoma. (Refer to the BAP1 section in the Melanoma section of this summary for more information.) Although the BCC penetrance in individuals with pathogenic variants in BAP1 is yet undescribed, there are several BAP1 families that report diagnoses of BCC.[32,33] In one study, pathogenic variant carriers from four families reported diagnoses of BCC. Tumor evaluation of BAP1 showed loss of BAP1 protein expression by immunohistochemistry in BCCs of two germline BAP1 pathogenic variant carriers but not in 53 sporadic BCCs.[32] A second report noted that four individuals from BAP1 families were diagnosed with a total of 19 BCCs. Complete loss of BAP1 nuclear expression was observed in 17 of 19 BCCs from these individuals but none of 22 control BCC specimens.[34] Loss of BAP1 nuclear expression was also reported in a series of 7 BCCs from individuals with loss of function BAP1 variants, but only in 1 of 31 sporadic BCCs.[35]

BCNS, also known as Gorlin Syndrome, Gorlin-Goltz syndrome, and nevoid BCC syndrome, is an autosomal dominant disorder with an estimated prevalence of 1 in 57,000 individuals.[36] The syndrome is notable for complete penetrance and high levels of variable expressivity, as evidenced by evaluation of individuals with identical genotypes but widely varying phenotypes.[27,37] The clinical features of BCNS differ more among families than within families.[38] BCNS is primarily associated with germline pathogenic variants in PTCH1, but families with this phenotype have also been associated with alterations in PTCH2 and SUFU.[39-41]

As detailed above, PTCH1 provides both developmental and regulatory guidance; spontaneous or inherited germline pathogenic variants of PTCH1 in BCNS may result in a wide spectrum of potentially diagnostic physical findings. The BCNS pathogenic variant has been localized to chromosome 9q22.3-q31, with a maximum logarithm of the odd (LOD) score of 3.597 and 6.457 at markers D9S12 and D9S53.[36] The resulting haploinsufficiency of PTCH1 in BCNS has been associated with structural anomalies such as odontogenic keratocysts, with evaluation of the cyst lining revealing heterozygosity for PTCH1.[42] The development of BCC and other BCNS-associated malignancies is thought to arise from the classic two-hit suppressor gene model: baseline heterozygosity secondary to germline PTCH1 pathogenic variant as the first hit, with the second hit due to mutagen exposure such as UV or ionizing radiation.[43-47] However, haploinsufficiency or dominant negative isoforms have also been implicated for the inactivation of PTCH1.[48]

The diagnosis of BCNS is typically based upon characteristic clinical and radiologic examination findings. Several sets of clinical diagnostic criteria for BCNS are in use (refer to Table 1 for a comparison of these criteria).[49-52] Although each set of criteria has advantages and disadvantages, none of the sets have a clearly superior balance of sensitivity and specificity for identifying carriers of pathogenic variants. The BCNS Colloquium Group proposed criteria in 2011 that required 1 major criterion with molecular diagnosis, two major criteria without molecular diagnosis, or one major and two minor criteria without molecular diagnosis.[52] PTCH1 pathogenic variants are found in 60% to 85% of patients who meet clinical criteria.[53,54] Most notably, BCNS is associated with the formation of both benign and malignant neoplasms. The strongest benign neoplasm association is with ovarian fibromas, diagnosed in 14% to 24% of females affected by BCNS.[46,50,55] BCNS-associated ovarian fibromas are more likely to be bilateral and calcified than sporadic ovarian fibromas.[56] Ameloblastomas, aggressive tumors of the odontogenic epithelium, have also been proposed as a diagnostic criterion for BCNS, but most groups do not include it at this time.[57]

Other associated benign neoplasms include gastric hamartomatous polyps,[58] congenital pulmonary cysts,[59] cardiac fibromas,[60] meningiomas,[61-63] craniopharyngiomas,[64] fetal rhabdomyomas,[65] leiomyomas,[66] mesenchymomas,[67] and nasal dermoid tumors. Development of meningiomas and ependymomas occurring postradiation therapy has been documented in the general pediatric population; radiation therapy for syndrome-associated intracranial processes may be partially responsible for a subset of these benign tumors in individuals with BCNS.[68-70] In addition, radiation therapy of malignant medulloblastomas in the BCNS population may result in many cutaneous BCCs in the radiation ports. Similarly, treatment of BCC of the skin with radiation therapy may result in induction of large numbers of additional BCCs.[45,46,66]

The diagnostic criteria for BCNS are described in Table 1 below.

Of greatest concern with BCNS are associated malignant neoplasms, the most common of which is BCC. BCC in individuals with BCNS may appear during childhood as small acrochordon -like lesions, while larger lesions demonstrate more classic cutaneous features.[71] Nonpigmented BCCs are more common than pigmented lesions.[72] The age at first BCC diagnosis associated with BCNS ranges from 3 to 53 years, with a mean age of 21.4 years; the vast majority of individuals are diagnosed with their first BCC before age 20 years.[50,55] Most BCCs are located on sun-exposed sites, but individuals with greater than 100 BCCs have a more uniform distribution of BCCs over the body.[72] Case series have suggested that up to 1 in 200 individuals with BCC demonstrate findings supportive of a diagnosis of BCNS.[36] BCNS has rarely been reported in individuals with darker skin pigmentation; however, significantly fewer BCCs are found in individuals of African or Mediterranean ancestry.[50,73,74] Despite the rarity of BCC in this population, reported cases document full expression of the noncutaneous manifestations of BCNS.[74] However, in individuals of African ancestry who have received radiation therapy, significant basal cell tumor burden has been reported within the radiation port distribution.[50,66] Thus, cutaneous pigmentation may protect against the mutagenic effects of UV but not against ionizing radiation.

Variants associated with an increased risk of BCC in the general population appear to modify the age of BCC onset in individuals with BCNS. A study of 125 individuals with BCNS found that a variant in MC1R (Arg151Cys) was associated with an early median age of onset of 27 years (95% CI, 2034), compared with individuals who did not carry the risk allele and had a median age of BCC of 34 years (95% CI, 3040) (hazard ratio [HR], 1.64; 95% CI, 1.042.58, P = .034). A variant in the TERT-CLPTM1L gene showed a similar effect, with individuals with the risk allele having a median age of BCC of 31 years (95% CI, 2837) relative to a median onset of 41 years (95% CI, 3248) in individuals who did not carry a risk allele (HR, 1.44; 95% CI, 1.081.93, P = .014).[75]

Many other malignancies have been associated with BCNS. Medulloblastoma carries the strongest association with BCNS and is diagnosed in 1% to 5% of BCNS cases. While BCNS-associated medulloblastoma is typically diagnosed between ages 2 and 3 years, sporadic medulloblastoma is usually diagnosed later in childhood, between the ages of 6 and 10 years.[46,50,55,76] A desmoplastic phenotype occurring around age 2 years is very strongly associated with BCNS and carries a more favorable prognosis than sporadic classic medulloblastoma.[77,78] Up to three times more males than females with BCNS are diagnosed with medulloblastoma.[79] As with other malignancies, treatment of medulloblastoma with ionizing radiation has resulted in numerous BCCs within the radiation field.[46,61] Other reported malignancies include ovarian carcinoma,[80] ovarian fibrosarcoma,[81,82] astrocytoma,[83] melanoma,[84] Hodgkin disease,[85,86] rhabdomyosarcoma,[87] and undifferentiated sinonasal carcinoma.[88]

Odontogenic keratocystsor keratocystic odontogenic tumors (KCOTs), as renamed by the World Health Organization working groupare one of the major features of BCNS.[89] Demonstration of clonal loss of heterozygosity (LOH) of common tumor suppressor genes, including PTCH1, supports the transition of terminology to reflect a neoplastic process.[42] Less than one-half of KCOTs from individuals with BCNS show LOH of PTCH1.[48,90] The tumors are lined with a thin squamous epithelium and a thin corrugated layer of parakeratin. Increased mitotic activity in the tumor epithelium and potential budding of the basal layer with formation of daughter cysts within the tumor wall may be responsible for the high rates of recurrence post simple enucleation.[89,91] In a recent case series of 183 consecutively excised KCOTs, 6% of individuals demonstrated an association with BCNS.[89] A study that analyzed the rate of PTCH1 pathogenic variants in BCNS-associated KCOTs found that 11 of 17 individuals carried a germline PTCH1 pathogenic variant and an additional 3 individuals had somatic pathogenic variants in this gene.[92] Individuals with germline PTCH1 pathogenic variants had an early age of KCOT presentation. KCOTs occur in 65% to 100% of individuals with BCNS,[50,93] with higher rates of occurrence in young females.[94]

Palmoplantar pits are another major finding in BCC and occur in 70% to 80% of individuals with BCNS.[55] When these pits occur together with early-onset BCC and/or KCOTs, they are considered diagnostic for BCNS.[95]

Several characteristic radiologic findings have been associated with BCNS, including lamellar calcification of falx cerebri;[96,97] fused, splayed or bifid ribs;[98] and flame-shaped lucencies or pseudocystic bone lesions of the phalanges, carpal, tarsal, long bones, pelvis, and calvaria.[54] Imaging for rib abnormalities may be useful in establishing the diagnosis in younger children, who may have not yet fully manifested a diagnostic array on physical examination.

Table 2 summarizes the frequency and median age of onset of nonmalignant findings associated with BCNS.

Individuals with PTCH2 pathogenic variants may have a milder phenotype of BCNS than those with PTCH1 variants. Characteristic features such as palmar/plantar pits, macrocephaly, falx calcification, hypertelorism, and coarse face may be absent in these individuals.[99]

A 9p22.3 microdeletion syndrome that includes the PTCH1 locus has been described in ten children.[100] All patients had facial features typical of BCNS, including a broad forehead, but they had other features variably including craniosynostosis, hydrocephalus, macrosomia, and developmental delay. At the time of the report, none had basal cell skin cancer. On the basis of their hemizygosity of the PTCH1 gene, these patients are presumably at an increased risk of basal cell skin cancer.

Germline pathogenic variants in SUFU, a major negative regulator of the hedgehog pathway, have been identified in a small number of individuals with a clinical phenotype resembling that of BCNS.[40,41] These pathogenic variants were first identified in individuals with childhood medulloblastoma,[101] and the incidence of medulloblastoma appears to be much higher in individuals with BCNS associated with SUFU pathogenic variants than in those with PTCH1 variants.[40] SUFU pathogenic variants may also be associated with an increased predisposition to meningioma.[63,102] Conversely, odontogenic jaw keratocysts appear less frequently in this population. Some clinical laboratories offer genetic testing for SUFU pathogenic variants for individuals with BCNS who do not have an identifiable PTCH1 variant.

Rombo syndrome, a very rare probably autosomal dominant genetic disorder associated with BCC, has been outlined in three case series in the literature.[103-105] The cutaneous examination is within normal limits until age 7 to 10 years, with the development of distinctive cyanotic erythema of the lips, hands, and feet and early atrophoderma vermiculatum of the cheeks, with variable involvement of the elbows and dorsal hands and feet.[103] Development of BCC occurs in the fourth decade.[103] A distinctive grainy texture to the skin, secondary to interspersed small, yellowish, follicular-based papules and follicular atrophy, has been described.[103,105] Missing, irregularly distributed, and/or misdirected eyelashes and eyebrows are another associated finding.[103,104] The genetic basis of Rombo syndrome is not known.

Bazex-Dupr-Christol syndrome, another rare genodermatosis associated with development of BCC, has more thorough documentation in the literature than Rombo syndrome. Inheritance is accomplished in an X-linked dominant fashion, with no reported male-to-male transmission.[106-108] Regional assignment of the locus of interest to chromosome Xq24-q27 is associated with a maximum LOD score of 5.26 with the DXS1192 locus.[109] Further work has narrowed the potential location to an 11.4-Mb interval on chromosome Xq25-27; however, the causative gene remains unknown.[110]

Characteristic physical findings include hypotrichosis, hypohidrosis, milia, follicular atrophoderma of the cheeks, and multiple BCC, which manifest in the late second decade to early third decade.[106] Documented hair changes with Bazex-Dupr-Christol syndrome include reduced density of scalp and body hair, decreased melanization,[111] a twisted/flattened appearance of the hair shaft on electron microscopy,[112] and increased hair shaft diameter on polarizing light microscopy.[108] The milia, which may be quite distinctive in childhood, have been reported to regress or diminish substantially at puberty.[108] Other reported findings in association with this syndrome include trichoepitheliomas; hidradenitis suppurativa; hypoplastic alae; and a prominent columella, the fleshy terminal portion of the nasal septum.[113,114]

A rare subtype of epidermolysis bullosa simplex (EBS), Dowling-Meara (EBS-DM), is primarily inherited in an autosomal dominant fashion and is associated with pathogenic variants in either keratin-5 (KRT5) or keratin-14 (KRT14).[115] EBS-DM is one of the most severe types of EBS and occasionally results in mortality in early childhood.[116] One report cites an incidence of BCC of 44% by age 55 years in this population.[117] Individuals who inherit two EBS pathogenic variants may present with a more severe phenotype.[118] Other less phenotypically severe subtypes of EBS can also be caused by pathogenic variants in either KRT5 or KRT14.[115] Approximately 75% of individuals with a clinical diagnosis of EBS (regardless of subtype) have KRT5 or KRT14 pathogenic variants.[119]

Characteristics of hereditary syndromes associated with a predisposition to BCC are described in Table 3 below.

(Refer to the Brooke-Spiegler Syndrome, Multiple Familial Trichoepithelioma, and Familial Cylindromatosis section in the Rare Skin Cancer Syndromes section of this summary for more information about Brooke-Spiegler syndrome.)

As detailed further below, the U.S. Preventive Services Task Force does not recommend regular screening for the early detection of any cutaneous malignancies, including BCC. However, once BCC is detected, the National Comprehensive Cancer Network guidelines of care for NMSCs recommends complete skin examinations every 6 to 12 months for life.[130]

The BCNS Colloquium Group has proposed guidelines for the surveillance of individuals with BCNS (see Table 4).

Level of evidence: 5

Avoidance of excessive cumulative and sporadic sun exposure is important in reducing the risk of BCC, along with other cutaneous malignancies. Scheduling activities outside of the peak hours of UV radiation, utilizing sun-protective clothing and hats, using sunscreen liberally, and strictly avoiding tanning beds are all reasonable steps towards minimizing future risk of skin cancer.[131] For patients with particular genetic susceptibility (such as BCNS), avoidance or minimization of ionizing radiation is essential to reducing future tumor burden.

Level of evidence: 2aii

The role of various systemic retinoids, including isotretinoin and acitretin, has been explored in the chemoprevention and treatment of multiple BCCs, particularly in BCNS patients. In one study of isotretinoin use in 12 patients with multiple BCCs, including 5 patients with BCNS, tumor regression was noted, with decreasing efficacy as the tumor diameter increased.[132] However, the results were insufficient to recommend use of systemic retinoids for treatment of BCC. Three additional patients, including one with BCNS, were followed long-term for evaluation of chemoprevention with isotretinoin, demonstrating significant decrease in the number of tumors per year during treatment.[132] Although the rate of tumor development tends to increase sharply upon discontinuation of systemic retinoid therapy, in some patients the rate remains lower than their pretreatment rate, allowing better management and control of their cutaneous malignancies.[132-134] In summary, the use of systemic retinoids for chemoprevention of BCC is reasonable in high-risk patients, including patients with xeroderma pigmentosum, as discussed in the Squamous Cell Carcinoma section of this summary.

A patients cumulative and evolving tumor load should be evaluated carefully in light of the potential long-term use of a medication class with cumulative and idiosyncratic side effects. Given the possible side-effect profile, systemic retinoid use is best managed by a practitioner with particular expertise and comfort with the medication class. However, for all potentially childbearing women, strict avoidance of pregnancy during the systemic retinoid courseand for 1 month after completion of isotretinoin and 3 years after completion of acitretinis essential to avoid potentially fatal and devastating fetal malformations.

Level of evidence (retinoids): 2aii

In a phase II study of 41 patients with BCNS, vismodegib (an inhibitor of the hedgehog pathway) has been shown to reduce the per-patient annual rate of new BCCs requiring surgery.[135] Existing BCCs also regressed for these patients during daily treatment with 150 mg of oral vismodegib. While patients treated had visible regression of their tumors, biopsy demonstrated residual microscopic malignancies at the site, and tumors progressed after the discontinuation of the therapy. Adverse effects included taste disturbance, muscle cramps, hair loss, and weight loss and led to discontinuation of the medication in 54% of subjects. Based on the side-effect profile and rate of disease recurrence after discontinuation of the medication, additional study regarding optimal dosing of vismodegib is ongoing.

Level of evidence (vismodegib): 1aii

A phase III, double-blind, placebo-controlled clinical trial evaluated the effects of oral nicotinamide (vitamin B3) in 386 individuals with a history of at least two NMSCs within 5 years before study enrollment.[136] After 12 months of treatment, those taking nicotinamide 500 mg twice daily had a 20% reduction in the incidence of new BCCs (95% CI, 6%39%; P = .12). The rate of new NMSCs was 23% lower in the nicotinamide group (95% CI, 438; P =.02) than in the placebo group. No clinically significant differences in adverse events were observed between the two groups, and there was no evidence of benefit after discontinuation of nicotinamide. Of note, this study was not conducted in a population with an identified genetic predisposition to BCC.

Level of evidence (nicotinamide): 1aii

Treatment of individual BCCs in BCNS is generally the same as for sporadic basal cell cancers. Due to the large number of lesions on some patients, this can present a surgical challenge. Field therapy with imiquimod or photodynamic therapy are attractive options, as they can treat multiple tumors simultaneously.[137,138] However, given the radiosensitivity of patients with BCNS, radiation as a therapeutic option for large tumors should be avoided.[50] There are no randomized trials, but the isolated case reports suggest that field therapy has similar results as in sporadic basal cell cancer, with higher success rates for superficial cancers than for nodular cancers.[137,138]

Consensus guidelines for the use of methylaminolevulinate photodynamic therapy in BCNS recommend that this modality may best be used for superficial BCC of all sizes and for nodular BCC less than 2 mm thick.[139] Monthly therapy with photodynamic therapy may be considered for these patients as clinically indicated.

Level of evidence (imiquimod and photodynamic therapy): 4

Topical treatment with LDE225, a Smoothened agonist, has also been investigated for the treatment of BCC in a small number of patients with BCNS with promising results;[140] however, this medication is not approved in this formulation by the U.S. Food and Drug Administration.

Level of evidence (LDE225): 1

In addition to its effects on the prevention of BCCs in patients with BCNS, vismodegib may also have a palliative effect on KCOTs found in this population. An initial report indicated that the use of GDC-0449, the hedgehog pathway inhibitor now known as vismodegib, resulted in resolution of KCOTs in one patient with BCNS.[141] Another small study found that four of six patients who took 150 mg of vismodegib daily had a reduction in the size of KCOTs.[142] None of the six patients in this study had new KCOTs or an increase in the size of existing KCOTs while being treated, and one patient had a sustained response that lasted 9 months after treatment was discontinued.

Level of evidence (vismodegib): 3diii

Squamous cell carcinoma (SCC) is the second most common type of skin cancer and accounts for approximately 20% of cutaneous malignancies. Although most cancer registries do not include information on the incidence of nonmelanoma skin cancer (NMSC), annual incidence estimates range from 1 million to 5.4 million cases in the United States.[1,2]

Mortality is rare from this cancer; however, the morbidity and costs associated with its treatment are considerable.

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types; however, different patterns of sun exposure are associated with each major type of skin cancer.

Unlike basal cell carcinoma (BCC), SCC is associated with chronic exposure, rather than intermittent intense exposure to ultraviolet (UV) radiation. Occupational exposure is the characteristic pattern of sun exposure linked with SCC.[3] A case-control study in southern Europe showed increased risk of SCC when lifetime sun exposure exceeded 70,000 hours. People whose lifetime sun exposure equaled or exceeded 200,000 hours had an odds ratio (OR) 8 to 9 times that of the reference group.[4] A Canadian case-control study did not find an association between cumulative lifetime sun exposure and SCC; however, sun exposure in the 10 years before diagnosis and occupational exposure were found to be risk factors.[5]

In addition to environmental radiation, exposure to therapeutic radiation is another risk factor for SCC. Individuals with skin disorders treated with psoralen and ultraviolet-A radiation (PUVA) had a threefold to sixfold increase in SCC.[6] This effect appears to be dose-dependent, as only 7% of individuals who underwent fewer than 200 treatments had SCC, compared with more than 50% of those who underwent more than 400 treatments.[7] Therapeutic use of ultraviolet-B (UVB) radiation has also been shown to cause a mild increase in SCC (adjusted incidence rate ratio, 1.37).[8] Devices such as tanning beds also emit UV radiation and have been associated with increased SCC risk, with a reported OR of 2.5 (95% confidence interval [CI], 1.73.8).[9]

Investigation into the effect of ionizing radiation on SCC carcinogenesis has yielded conflicting results. One population-based case-control study found that patients who had undergone therapeutic radiation therapy had an increased risk of SCC at the site of previous radiation (OR, 2.94), compared with individuals who had not undergone radiation treatments.[10] Cohort studies of radiology technicians, atomic-bomb survivors, and survivors of childhood cancers have not shown an increased risk of SCC, although the incidence of BCC was increased in all of these populations.[11-13] For those who develop SCC at previously radiated sites that are not sun-exposed, the latent period appears to be quite long; these cancers may be diagnosed years or even decades after the radiation exposure.[14]

The effect of other types of radiation, such as cosmic radiation, is also controversial. Pilots and flight attendants have a reported incidence of SCC that ranges between 2.1 and 9.9 times what would be expected; however, the overall cancer incidence is not consistently elevated. Some attribute the high rate of NMSCs in airline flight personnel to cosmic radiation, while others suspect lifestyle factors.[15-20]

Like BCCs, SCCs appear to be associated with exposure to arsenic in drinking water and combustion products.[21,22] However, this association may hold true only for the highest levels of arsenic exposure. Individuals who had toenail concentrations of arsenic above the 97th percentile were found to have an approximately twofold increase in SCC risk.[23] For arsenic, the latency period can be lengthy; invasive SCC has been found to develop at an average of 20 years after exposure.[24]

Current or previous cigarette smoking has been associated with a 1.5-fold to 2-fold increase in SCC risk,[25-27] although one large study showed no change in risk.[28] Available evidence suggests that the effect of smoking on cancer risk seems to be greater for SCC than for BCC.

Additional reports have suggested weak associations between SCC and exposure to insecticides, herbicides, or fungicides.[29]

Like melanoma and BCC, SCC occurs more frequently in individuals with lighter skin than in those with darker skin.[3,30] A case-control study of 415 cases and 415 controls showed similar findings; relative to Fitzpatrick Type I skin, individuals with increasingly darker skin had decreased risks of skin cancer (ORs, 0.6, 0.3, and 0.1, for Fitzpatrick Types II, III, and IV, respectively).[31] (Refer to the Pigmentary characteristics section in the Melanoma section of this summary for a more detailed discussion of skin phenotypes based upon pigmentation.) The same study found that blue eyes and blond/red hair were also associated with increased risks of SCC, with crude ORs of 1.7 (95% CI, 1.22.3) for blue eyes, 1.5 (95% CI, 1.12.1) for blond hair, and 2.2 (95% CI, 1.53.3) for red hair.

However, SCC can also occur in individuals with darker skin. An Asian registry based in Singapore reported an increase in skin cancer in that geographic area, with an incidence rate of 8.9 per 100,000 person-years. Incidence of SCC, however, was shown to be on the decline.[30] SCC is the most common form of skin cancer in black individuals in the United States and in certain parts of Africa; the mortality rate for this disease is relatively high in these populations.[32,33] Epidemiologic characteristics of, and prevention strategies for, SCC in those individuals with darker skin remain areas of investigation.

Freckling of the skin and reaction of the skin to sun exposure have been identified as other risk factors for SCC.[34] Individuals with heavy freckling on the forearm were found to have a 14-fold increase in SCC risk if freckling was present in adulthood, and an almost threefold risk if freckling was present in childhood.[34,35] The degree of SCC risk corresponded to the amount of freckling. In this study, the inability of the skin to tan and its propensity to burn were also significantly associated with risk of SCC (OR of 2.9 for severe burn and 3.5 for no tan).

The presence of scars on the skin can also increase the risk of SCC, although the process of carcinogenesis in this setting may take years or even decades. SCCs arising in chronic wounds are referred to as Marjolins ulcers. The mean time for development of carcinoma in these wounds is estimated at 26 years.[36] One case report documents the occurrence of cancer in a wound that was incurred 59 years earlier.[37]

Immunosuppression also contributes to the formation of NMSCs. Among solid-organ transplant recipients, the risk of SCC is 65 to 250 times higher, and the risk of BCC is 10 times higher than that observed in the general population, although the risks vary with transplant type.[38-41] NMSCs in high-risk patients (solid-organ transplant recipients and chronic lymphocytic leukemia patients) occur at a younger age, are more common and more aggressive, and have a higher risk of recurrence and metastatic spread than these cancers do in the general population.[42,43] Additionally, there is a high risk of second SCCs.[44,45] In one study, over 65% of kidney transplant recipients developed subsequent SCCs after their first diagnosis.[44] Among patients with an intact immune system, BCCs outnumber SCCs by a 4:1 ratio; in transplant patients, SCCs outnumber BCCs by a 2:1 ratio.

This increased risk has been linked to an interaction between the level of immunosuppression and UV radiation exposure. As the duration and dosage of immunosuppressive agents increase, so does the risk of cutaneous malignancy; this effect is reversed with decreasing the dosage of, or taking a break from, immunosuppressive agents. Heart transplant recipients, requiring the highest rates of immunosuppression, are at much higher risk of cutaneous malignancy than liver transplant recipients, in whom much lower levels of immunosuppression are needed to avoid rejection.[38,46,47] The risk appears to be highest in geographic areas with high UV exposure.[47] When comparing Australian and Dutch organ transplant populations, the Australian patients carried a fourfold increased risk of developing SCC and a fivefold increased risk of developing BCC.[48] This finding underlines the importance of rigorous sun avoidance, particularly among high-risk immunosuppressed individuals.

Link:
Genetics of Skin Cancer (PDQ)Health Professional Version ...

Genetically modified foods or GM foods, also known as genetically engineered foods, are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering. Genetic engineering techniques allow for the introduction of new traits as well as greater control over traits than previous methods such as selective breeding and mutation breeding.[1]

Commercial sale of genetically modified foods began in 1994, when Calgene first marketed its unsuccessful Flavr Savr delayed-ripening tomato.[2][3] Most food modifications have primarily focused on cash crops in high demand by farmers such as soybean, corn, canola, and cotton. Genetically modified crops have been engineered for resistance to pathogens and herbicides and for better nutrient profiles. GM livestock have been developed, although as of November 2013 none were on the market.[4]

There is a scientific consensus[5][6][7][8] that currently available food derived from GM crops poses no greater risk to human health than conventional food,[9][10][11][12][13] but that each GM food needs to be tested on a case-by-case basis before introduction.[14][15][16] Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe.[17][18][19][20] The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation.[21][22][23][24]

However, there are ongoing public concerns related to food safety, regulation, labelling, environmental impact, research methods, and the fact that some GM seeds are subject to intellectual property rights owned by corporations.[25]

Genetically modified foods, GM foods or genetically engineered foods, are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering as opposed to traditional cross breeding.[26][27] In the US, the Department of Agriculture (USDA) and the Food and Drug Administration (FDA) favor the use of "genetic engineering" over "genetic modification" as the more precise term; the USDA defines genetic modification to include "genetic engineering or other more traditional methods."[28][29]

According to the World Health Organization, "Genetically modified organisms (GMOs) can be defined as organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination. The technology is often called 'modern biotechnology' or 'gene technology', sometimes also 'recombinant DNA technology' or 'genetic engineering'. ... Foods produced from or using GM organisms are often referred to as GM foods."[26]

Human-directed genetic manipulation of food began with the domestication of plants and animals through artificial selection at about 10,500 to 10,100 BC.[30]:1 The process of selective breeding, in which organisms with desired traits (and thus with the desired genes) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification (GM).[30]:1[31]:1 With the discovery of DNA in the early 1900s and various advancements in genetic techniques through the 1970s[32] it became possible to directly alter the DNA and genes within food.

The first genetically modified plant was produced in 1983, using an antibiotic-resistant tobacco plant.[33] Genetically modified microbial enzymes were the first application of genetically modified organisms in food production and were approved in 1988 by the US Food and Drug Administration.[34] In the early 1990s, recombinant chymosin was approved for use in several countries.[34][35] Cheese had typically been made using the enzyme complex rennet that had been extracted from cows' stomach lining. Scientists modified bacteria to produce chymosin, which was also able to clot milk, resulting in cheese curds.[36]

The first genetically modified food approved for release was the Flavr Savr tomato in 1994.[2] Developed by Calgene, it was engineered to have a longer shelf life by inserting an antisense gene that delayed ripening.[37] China was the first country to commercialize a transgenic crop in 1993 with the introduction of virus-resistant tobacco.[38] In 1995, Bacillus thuringiensis (Bt) Potato was approved for cultivation, making it the first pesticide producing crop to be approved in the USA.[39] Other genetically modified crops receiving marketing approval in 1995 were: canola with modified oil composition, Bt maize, cotton resistant to the herbicide bromoxynil, Bt cotton, glyphosate-tolerant soybeans, virus-resistant squash, and another delayed ripening tomato.[2]

With the creation of golden rice in 2000, scientists had genetically modified food to increase its nutrient value for the first time.[40]

By 2010, 29 countries had planted commercialized biotech crops and a further 31 countries had granted regulatory approval for transgenic crops to be imported.[41] The US was the leading country in the production of GM foods in 2011, with twenty-five GM crops having received regulatory approval.[42] In 2015, 92% of corn, 94% of soybeans, and 94% of cotton produced in the US were genetically modified strains.[43]

The first genetically modified animal to be approved for food use was AquAdvantage salmon in 2015.[44] The salmon were transformed with a growth hormone-regulating gene from a Pacific Chinook salmon and a promoter from an ocean pout enabling it to grow year-round instead of only during spring and summer.[45]

In April 2016, a white button mushroom (Agaricus bisporus) modified using the CRISPR technique received de facto approval in the United States, after the USDA said it would not have to go through the agency's regulatory process. The agency considers the mushroom exempt because the editing process did not involve the introduction of foreign DNA.[46]

The most widely planted GMOs are designed to tolerate herbicides. By 2006 some weed populations had evolved to tolerate some of the same herbicides. Palmer amaranth is a weed that competes with cotton. A native of the southwestern US, it traveled east and was first found resistant to glyphosate in 2006, less than 10 years after GM cotton was introduced.[47][48][49]

Genetically engineered organisms are generated and tested in the laboratory for desired qualities. The most common modification is to add one or more genes to an organism's genome. Less commonly, genes are removed or their expression is increased or silenced or the number of copies of a gene is increased or decreased.

Once satisfactory strains are produced, the producer applies for regulatory approval to field-test them, called a "field release." Field-testing involves cultivating the plants on farm fields or growing animals in a controlled environment. If these field tests are successful, the producer applies for regulatory approval to grow and market the crop. Once approved, specimens (seeds, cuttings, breeding pairs, etc.) are cultivated and sold to farmers. The farmers cultivate and market the new strain. In some cases, the approval covers marketing but not cultivation.

According to the USDA, the number of field releases for genetically engineered organisms has grown from four in 1985 to an average of about 800 per year. Cumulatively, more than 17,000 releases had been approved through September 2013.[50]

Papaya was genetically modified to resist the ringspot virus. 'SunUp' is a transgenic red-fleshed Sunset papaya cultivar that is homozygous for the coat protein gene PRSV; 'Rainbow' is a yellow-fleshed F1 hybrid developed by crossing 'SunUp' and nontransgenic yellow-fleshed 'Kapoho'.[51] The New York Times stated, "in the early 1990s, Hawaiis papaya industry was facing disaster because of the deadly papaya ringspot virus. Its single-handed savior was a breed engineered to be resistant to the virus. Without it, the states papaya industry would have collapsed. Today, 80% of Hawaiian papaya is genetically engineered, and there is still no conventional or organic method to control ringspot virus."[52] The GM cultivar was approved in 1998.[53] In China, a transgenic PRSV-resistant papaya was developed by South China Agricultural University and was first approved for commercial planting in 2006; as of 2012 95% of the papaya grown in Guangdong province and 40% of the papaya grown in Hainan province was genetically modified.[54]

The New Leaf potato, a GM food developed using naturally occurring bacteria found in the soil known as Bacillus thuringiensis (Bt), was made to provide in-plant protection from the yield-robbing Colorado potato beetle.[55] The New Leaf potato, brought to market by Monsanto in the late 1990s, was developed for the fast food market. It was withdrawn in 2001 after retailers rejected it and food processors ran into export problems.[56]

As of 2005, about 13% of the Zucchini (a form of squash) grown in the US was genetically modified to resist three viruses; that strain is also grown in Canada.[57][58]

In 2011, BASF requested the European Food Safety Authority's approval for cultivation and marketing of its Fortuna potato as feed and food. The potato was made resistant to late blight by adding resistant genes blb1 and blb2 that originate from the Mexican wild potato Solanum bulbocastanum.[59][60] In February 2013, BASF withdrew its application.[61]

In 2013, the USDA approved the import of a GM pineapple that is pink in color and that "overexpresses" a gene derived from tangerines and suppress other genes, increasing production of lycopene. The plant's flowering cycle was changed to provide for more uniform growth and quality. The fruit "does not have the ability to propagate and persist in the environment once they have been harvested," according to USDA APHIS. According to Del Monte's submission, the pineapples are commercially grown in a "monoculture" that prevents seed production, as the plant's flowers aren't exposed to compatible pollen sources. Importation into Hawaii is banned for "plant sanitation" reasons.[62]

In 2014, the USDA approved a genetically modified potato developed by J.R. Simplot Company that contained ten genetic modifications that prevent bruising and produce less acrylamide when fried. The modifications eliminate specific proteins from the potatoes, via RNA interference, rather than introducing novel proteins.[63][64]

In February 2015 Arctic Apples were approved by the USDA,[65] becoming the first genetically modified apple approved for sale in the US.[66]Gene silencing is used to reduce the expression of polyphenol oxidase (PPO), thus preventing the fruit from browning.[67]

Corn used for food and ethanol has been genetically modified to tolerate various herbicides and to express a protein from Bacillus thuringiensis (Bt) that kills certain insects.[68] About 90% of the corn grown in the U.S. was genetically modified in 2010.[69] In the US in 2015, 81% of corn acreage contained the Bt trait and 89% of corn acreage contained the glyphosate-tolerant trait.[43] Corn can be processed into grits, meal and flour as an ingredient in pancakes, muffins, doughnuts, breadings and batters, as well as baby foods, meat products, cereals and some fermented products. Corn-based masa flour and masa dough are used in the production of taco shells, corn chips and tortillas.[70]

Genetically modified soybean has been modified to tolerate herbicides and produce healthier oils.[71] In 2015, 94% of soybean acreage in the U.S. was genetically modified to be glyphosate-tolerant.[43]

Starch or amylum is a polysaccharide produced by all green plants as an energy store. Pure starch is a white, tasteless and odourless powder. It consists of two types of molecules: the linear and helical amylose and the branched amylopectin. Depending on the plant, starch generally contains 20 to 25% amylose and 75 to 80% amylopectin by weight.[72]

Starch can be further modified to create modified starch for specific purposes,[73] including creation of many of the sugars in processed foods. They include:

Lecithin is a naturally occurring lipid. It can be found in egg yolks and oil-producing plants. it is an emulsifier and thus is used in many foods. Corn, soy and safflower oil are sources of lecithin, though the majority of lecithin commercially available is derived from soy.[74][75][76][pageneeded] Sufficiently processed lecithin is often undetectable with standard testing practices.[72][not in citation given] According to the FDA, no evidence shows or suggests hazard to the public when lecithin is used at common levels. Lecithin added to foods amounts to only 2 to 10 percent of the 1 to 5 g of phosphoglycerides consumed daily on average.[74][75] Nonetheless, consumer concerns about GM food extend to such products.[77][bettersourceneeded] This concern led to policy and regulatory changes in Europe in 2000,[citation needed] when Regulation (EC) 50/2000 was passed[78] which required labelling of food containing additives derived from GMOs, including lecithin.[citation needed] Because of the difficulty of detecting the origin of derivatives like lecithin with current testing practices, European regulations require those who wish to sell lecithin in Europe to employ a comprehensive system of Identity preservation (IP).[79][verification needed][80][pageneeded]

The US imports 10% of its sugar, while the remaining 90% is extracted from sugar beet and sugarcane. After deregulation in 2005, glyphosate-resistant sugar beet was extensively adopted in the United States. 95% of beet acres in the US were planted with glyphosate-resistant seed in 2011.[81] GM sugar beets are approved for cultivation in the US, Canada and Japan; the vast majority are grown in the US. GM beets are approved for import and consumption in Australia, Canada, Colombia, EU, Japan, Korea, Mexico, New Zealand, Philippines, Russian Federation and Singapore.[82] Pulp from the refining process is used as animal feed. The sugar produced from GM sugarbeets contains no DNA or proteinit is just sucrose that is chemically indistinguishable from sugar produced from non-GM sugarbeets.[72][83] Independent analyses conducted by internationally recognized laboratories found that sugar from Roundup Ready sugar beets is identical to the sugar from comparably grown conventional (non-Roundup Ready) sugar beets. And, like all sugar, sugar from Roundup Ready sugar beets contains no genetic material or detectable protein (including the protein that provides glyphosate tolerance).[84]

Most vegetable oil used in the US is produced from GM crops canola,[85]corn,[86][87]cotton[88] and soybeans.[89] Vegetable oil is sold directly to consumers as cooking oil, shortening and margarine[90] and is used in prepared foods. There is a vanishingly small amount of protein or DNA from the original crop in vegetable oil.[72][91] Vegetable oil is made of triglycerides extracted from plants or seeds and then refined and may be further processed via hydrogenation to turn liquid oils into solids. The refining process[92] removes all, or nearly all non-triglyceride ingredients.[93] Medium-chain triglycerides (MCTs) offer an alternative to conventional fats and oils. The length of a fatty acid influences its fat absorption during the digestive process. Fatty acids in the middle position on the glycerol molecules appear to be absorbed more easily and influence metabolism more than fatty acids on the end positions. Unlike ordinary fats, MCTs are metabolized like carbohydrates. They have exceptional oxidative stability, and prevent foods from turning rancid readily.[94]

Livestock and poultry are raised on animal feed, much of which is composed of the leftovers from processing crops, including GM crops. For example, approximately 43% of a canola seed is oil. What remains after oil extraction is a meal that becomes an ingredient in animal feed and contains canola protein.[95] Likewise, the bulk of the soybean crop is grown for oil and meal. The high-protein defatted and toasted soy meal becomes livestock feed and dog food. 98% of the US soybean crop goes for livestock feed.[96][97] In 2011, 49% of the US maize harvest was used for livestock feed (including the percentage of waste from distillers grains).[98] "Despite methods that are becoming more and more sensitive, tests have not yet been able to establish a difference in the meat, milk, or eggs of animals depending on the type of feed they are fed. It is impossible to tell if an animal was fed GM soy just by looking at the resulting meat, dairy, or egg products. The only way to verify the presence of GMOs in animal feed is to analyze the origin of the feed itself."[99]

A 2012 literature review of studies evaluating the effect of GM feed on the health of animals did not find evidence that animals were adversely affected, although small biological differences were occasionally found. The studies included in the review ranged from 90 days to two years, with several of the longer studies considering reproductive and intergenerational effects.[100]

Rennet is a mixture of enzymes used to coagulate milk into cheese. Originally it was available only from the fourth stomach of calves, and was scarce and expensive, or was available from microbial sources, which often produced unpleasant tastes. Genetic engineering made it possible to extract rennet-producing genes from animal stomachs and insert them into bacteria, fungi or yeasts to make them produce chymosin, the key enzyme.[101][102] The modified microorganism is killed after fermentation. Chymosin is isolated from the fermentation broth, so that the Fermentation-Produced Chymosin (FPC) used by cheese producers has an amino acid sequence that is identical to bovine rennet.[103] The majority of the applied chymosin is retained in the whey. Trace quantities of chymosin may remain in cheese.[103]

FPC was the first artificially produced enzyme to be approved by the US Food and Drug Administration.[34][35] FPC products have been on the market since 1990 and as of 2015 had yet to be surpassed in commercial markets.[104] In 1999, about 60% of US hard cheese was made with FPC.[105] Its global market share approached 80%.[106] By 2008, approximately 80% to 90% of commercially made cheeses in the US and Britain were made using FPC.[103]

In some countries, recombinant (GM) bovine somatotropin (also called rBST, or bovine growth hormone or BGH) is approved for administration to increase milk production. rBST may be present in milk from rBST treated cows, but it is destroyed in the digestive system and even if directly injected into the human bloodstream, has no observable effect on humans.[107][108][109] The FDA, World Health Organization, American Medical Association, American Dietetic Association and the National Institutes of Health have independently stated that dairy products and meat from rBST-treated cows are safe for human consumption.[110] However, on 30 September 2010, the United States Court of Appeals, Sixth Circuit, analyzing submitted evidence, found a "compositional difference" between milk from rBGH-treated cows and milk from untreated cows.[111][112] The court stated that milk from rBGH-treated cows has: increased levels of the hormone Insulin-like growth factor 1 (IGF-1); higher fat content and lower protein content when produced at certain points in the cow's lactation cycle; and more somatic cell counts, which may "make the milk turn sour more quickly."[112]

Genetically modified livestock are organisms from the group of cattle, sheep, pigs, goats, birds, horses and fish kept for human consumption, whose genetic material (DNA) has been altered using genetic engineering techniques. In some cases, the aim is to introduce a new trait to the animals which does not occur naturally in the species, i.e. transgenesis.

A 2003 review published on behalf of Food Standards Australia New Zealand examined transgenic experimentation on terrestrial livestock species as well as aquatic species such as fish and shellfish. The review examined the molecular techniques used for experimentation as well as techniques for tracing the transgenes in animals and products as well as issues regarding transgene stability.[113]

Some mammals typically used for food production have been modified to produce non-food products, a practice sometimes called Pharming.

A GM salmon, awaiting regulatory approval[114][115][116] since 1997,[117] was approved for human consumption by the American FDA in November 2015, to be raised in specific land-based hatcheries in Canada and Panama.[118]

The use of genetically modified food-grade organisms as recombinant vaccine expression hosts and delivery vehicles can open new avenues for vaccinology. Considering that oral immunization is a beneficial approach in terms of costs, patient comfort, and protection of mucosal tissues, the use of food-grade organisms can lead to highly advantageous vaccines in terms of costs, easy administration, and safety. The organisms currently used for this purpose are bacteria (Lactobacillus and Bacillus), yeasts, algae, plants, and insect species. Several such organisms are under clinical evaluation, and the current adoption of this technology by the industry indicates a potential to benefit global healthcare systems.[119]

There is a scientific consensus[120][121][122][123] that currently available food derived from GM crops poses no greater risk to human health than conventional food,[124][125][126][127][128] but that each GM food needs to be tested on a case-by-case basis before introduction.[129][130][131] Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe.[132][133][134][135]

Opponents claim that long-term health risks have not been adequately assessed and propose various combinations of additional testing, labeling[136] or removal from the market.[137][138][139][140] The advocacy group European Network of Scientists for Social and Environmental Responsibility (ENSSER), disputes the claim that "science" supports the safety of current GM foods, proposing that each GM food must be judged on case-by-case basis.[141] The Canadian Association of Physicians for the Environment called for removing GM foods from the market pending long term health studies.[137] Multiple disputed studies have claimed health effects relating to GM foods or to the pesticides used with them.[142]

The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation.[143][144][145][146] Countries such as the United States, Canada, Lebanon and Egypt use substantial equivalence to determine if further testing is required, while many countries such as those in the European Union, Brazil and China only authorize GMO cultivation on a case-by-case basis. In the U.S. the FDA determined that GMO's are "Generally Recognized as Safe" (GRAS) and therefore do not require additional testing if the GMO product is substantially equivalent to the non-modified product.[147] If new substances are found, further testing may be required to satisfy concerns over potential toxicity, allergenicity, possible gene transfer to humans or genetic outcrossing to other organisms.[26]

Government regulation of GMO development and release varies widely between countries. Marked differences separate GMO regulation in the U.S. and GMO regulation in the European Union.[148] Regulation also varies depending on the intended product's use. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety.[149]

In the U.S., three government organizations regulate GMOs. The FDA checks the chemical composition of organisms for potential allergens. The United States Department of Agriculture (USDA) supervises field testing and monitors the distribution of GM seeds. The United States Environmental Protection Agency (EPA) is responsible for monitoring pesticide usage, including plants modified to contain proteins toxic to insects. Like USDA, EPA also oversees field testing and the distribution of crops that have had contact with pesticides to ensure environmental safety.[150][bettersourceneeded] In 2015 the Obama administration announced that it would update the way the government regulated GM crops.[151]

In 1992 FDA published "Statement of Policy: Foods derived from New Plant Varieties." This statement is a clarification of FDA's interpretation of the Food, Drug, and Cosmetic Act with respect to foods produced from new plant varieties developed using recombinant deoxyribonucleic acid (rDNA) technology. FDA encouraged developers to consult with the FDA regarding any bioengineered foods in development. The FDA says developers routinely do reach out for consultations. In 1996 FDA updated consultation procedures.[152][153]

As of 2015, 64 countries require labeling of GMO products in the marketplace.[154]

US and Canadian national policy is to require a label only given significant composition differences or documented health impacts, although some individual US states (Vermont, Connecticut and Maine) enacted laws requiring them.[155][156][157][158] In July 2016, Public Law 114-214 was enacted to regulate labeling of GMO food on a national basis.

In some jurisdictions, the labeling requirement depends on the relative quantity of GMO in the product. A study that investigated voluntary labeling in South Africa found that 31% of products labeled as GMO-free had a GM content above 1.0%.[159]

In Europe all food (including processed food) or feed that contains greater than 0.9% GMOs must be labelled.[160]

Testing on GMOs in food and feed is routinely done using molecular techniques such as PCR and bioinformatics.[161]

In a January 2010 paper, the extraction and detection of DNA along a complete industrial soybean oil processing chain was described to monitor the presence of Roundup Ready (RR) soybean: "The amplification of soybean lectin gene by end-point polymerase chain reaction (PCR) was successfully achieved in all the steps of extraction and refining processes, until the fully refined soybean oil. The amplification of RR soybean by PCR assays using event-specific primers was also achieved for all the extraction and refining steps, except for the intermediate steps of refining (neutralisation, washing and bleaching) possibly due to sample instability. The real-time PCR assays using specific probes confirmed all the results and proved that it is possible to detect and quantify genetically modified organisms in the fully refined soybean oil. To our knowledge, this has never been reported before and represents an important accomplishment regarding the traceability of genetically modified organisms in refined oils."[162]

According to Thomas Redick, detection and prevention of cross-pollination is possible through the suggestions offered by the Farm Service Agency (FSA) and Natural Resources Conservation Service (NRCS). Suggestions include educating farmers on the importance of coexistence, providing farmers with tools and incentives to promote coexistence, conduct research to understand and monitor gene flow, provide assurance of quality and diversity in crops, provide compensation for actual economic losses for farmers.[163]

The genetically modified foods controversy consists of a set of disputes over the use of food made from genetically modified crops. The disputes involve consumers, farmers, biotechnology companies, governmental regulators, non-governmental organizations, environmental and political activists and scientists. The major disagreements include whether GM foods can be safely consumed, harm the environment and/or are adequately tested and regulated.[138][164] The objectivity of scientific research and publications has been challenged.[137] Farming-related disputes include the use and impact of pesticides, seed production and use, side effects on non-GMO crops/farms,[165] and potential control of the GM food supply by seed companies.[137]

The conflicts have continued since GM foods were invented. They have occupied the media, the courts, local, regional and national governments and international organizations.

The literature about Biodiversity and the GE food/feed consumption has sometimes resulted in animated debate regarding the suitability of the experimental designs, the choice of the statistical methods or the public accessibility of data. Such debate, even if positive and part of the natural process of review by the scientific community, has frequently been distorted by the media and often used politically and inappropriately in anti-GE crops campaigns.

Domingo, Jos L.; Bordonaba, Jordi Gin (2011). "A literature review on the safety assessment of genetically modified plants" (PDF). Environment International. 37: 734742. doi:10.1016/j.envint.2011.01.003. PMID21296423. In spite of this, the number of studies specifically focused on safety assessment of GM plants is still limited. However, it is important to remark that for the first time, a certain equilibrium in the number of research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was observed. Moreover, it is worth mentioning that most of the studies demonstrating that GM foods are as nutritional and safe as those obtained by conventional breeding, have been performed by biotechnology companies or associates, which are also responsible of commercializing these GM plants. Anyhow, this represents a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies.

Krimsky, Sheldon (2015). "An Illusory Consensus behind GMO Health Assessment" (PDF). Science, Technology, & Human Values. 40: 132. doi:10.1177/0162243915598381. I began this article with the testimonials from respected scientists that there is literally no scientific controversy over the health effects of GMOs. My investigation into the scientific literature tells another story.

And contrast:

Panchin, Alexander Y.; Tuzhikov, Alexander I. (January 14, 2016). "Published GMO studies find no evidence of harm when corrected for multiple comparisons". Critical Reviews in Biotechnology: 15. doi:10.3109/07388551.2015.1130684. ISSN0738-8551. PMID26767435. Here, we show that a number of articles some of which have strongly and negatively influenced the public opinion on GM crops and even provoked political actions, such as GMO embargo, share common flaws in the statistical evaluation of the data. Having accounted for these flaws, we conclude that the data presented in these articles does not provide any substantial evidence of GMO harm.

The presented articles suggesting possible harm of GMOs received high public attention. However, despite their claims, they actually weaken the evidence for the harm and lack of substantial equivalency of studied GMOs. We emphasize that with over 1783 published articles on GMOs over the last 10 years it is expected that some of them should have reported undesired differences between GMOs and conventional crops even if no such differences exist in reality.

and

Yang, Y.T.; Chen, B. (2016). "Governing GMOs in the USA: science, law and public health". Journal of the Science of Food and Agriculture. 96: 18511855. doi:10.1002/jsfa.7523. PMID26536836. It is therefore not surprising that efforts to require labeling and to ban GMOs have been a growing political issue in the USA (citing Domingo and Bordonaba, 2011).

Overall, a broad scientific consensus holds that currently marketed GM food poses no greater risk than conventional food... Major national and international science and medical associations have stated that no adverse human health effects related to GMO food have been reported or substantiated in peer-reviewed literature to date.

Despite various concerns, today, the American Association for the Advancement of Science, the World Health Organization, and many independent international science organizations agree that GMOs are just as safe as other foods. Compared with conventional breeding techniques, genetic engineering is far more precise and, in most cases, less likely to create an unexpected outcome.

Pinholster, Ginger (October 25, 2012). "AAAS Board of Directors: Legally Mandating GM Food Labels Could "Mislead and Falsely Alarm Consumers"". American Association for the Advancement of Science. Retrieved February 8, 2016.

"REPORT 2 OF THE COUNCIL ON SCIENCE AND PUBLIC HEALTH (A-12): Labeling of Bioengineered Foods" (PDF). American Medical Association. 2012. Retrieved March 19, 2016. Bioengineered foods have been consumed for close to 20 years, and during that time, no overt consequences on human health have been reported and/or substantiated in the peer-reviewed literature.

GM foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved. Continuous application of safety assessments based on the Codex Alimentarius principles and, where appropriate, adequate post market monitoring, should form the basis for ensuring the safety of GM foods.

"Genetically modified foods and health: a second interim statement" (PDF). British Medical Association. March 2004. Retrieved March 21, 2016. In our view, the potential for GM foods to cause harmful health effects is very small and many of the concerns expressed apply with equal vigour to conventionally derived foods. However, safety concerns cannot, as yet, be dismissed completely on the basis of information currently available.

When seeking to optimise the balance between benefits and risks, it is prudent to err on the side of caution and, above all, learn from accumulating knowledge and experience. Any new technology such as genetic modification must be examined for possible benefits and risks to human health and the environment. As with all novel foods, safety assessments in relation to GM foods must be made on a case-by-case basis.

Members of the GM jury project were briefed on various aspects of genetic modification by a diverse group of acknowledged experts in the relevant subjects. The GM jury reached the conclusion that the sale of GM foods currently available should be halted and the moratorium on commercial growth of GM crops should be continued. These conclusions were based on the precautionary principle and lack of evidence of any benefit. The Jury expressed concern over the impact of GM crops on farming, the environment, food safety and other potential health effects.

The Royal Society review (2002) concluded that the risks to human health associated with the use of specific viral DNA sequences in GM plants are negligible, and while calling for caution in the introduction of potential allergens into food crops, stressed the absence of evidence that commercially available GM foods cause clinical allergic manifestations. The BMA shares the view that that there is no robust evidence to prove that GM foods are unsafe but we endorse the call for further research and surveillance to provide convincing evidence of safety and benefit.

The literature about Biodiversity and the GE food/feed consumption has sometimes resulted in animated debate regarding the suitability of the experimental designs, the choice of the statistical methods or the public accessibility of data. Such debate, even if positive and part of the natural process of review by the scientific community, has frequently been distorted by the media and often used politically and inappropriately in anti-GE crops campaigns.

Domingo, Jos L.; Bordonaba, Jordi Gin (2011). "A literature review on the safety assessment of genetically modified plants" (PDF). Environment International. 37: 734742. doi:10.1016/j.envint.2011.01.003. PMID21296423. In spite of this, the number of studies specifically focused on safety assessment of GM plants is still limited. However, it is important to remark that for the first time, a certain equilibrium in the number of research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was observed. Moreover, it is worth mentioning that most of the studies demonstrating that GM foods are as nutritional and safe as those obtained by conventional breeding, have been performed by biotechnology companies or associates, which are also responsible of commercializing these GM plants. Anyhow, this represents a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies.

Krimsky, Sheldon (2015). "An Illusory Consensus behind GMO Health Assessment" (PDF). Science, Technology, & Human Values. 40: 132. doi:10.1177/0162243915598381. I began this article with the testimonials from respected scientists that there is literally no scientific controversy over the health effects of GMOs. My investigation into the scientific literature tells another story.

And contrast:

Panchin, Alexander Y.; Tuzhikov, Alexander I. (January 14, 2016). "Published GMO studies find no evidence of harm when corrected for multiple comparisons". Critical Reviews in Biotechnology: 15. doi:10.3109/07388551.2015.1130684. ISSN0738-8551. PMID26767435. Here, we show that a number of articles some of which have strongly and negatively influenced the public opinion on GM crops and even provoked political actions, such as GMO embargo, share common flaws in the statistical evaluation of the data. Having accounted for these flaws, we conclude that the data presented in these articles does not provide any substantial evidence of GMO harm.

The presented articles suggesting possible harm of GMOs received high public attention. However, despite their claims, they actually weaken the evidence for the harm and lack of substantial equivalency of studied GMOs. We emphasize that with over 1783 published articles on GMOs over the last 10 years it is expected that some of them should have reported undesired differences between GMOs and conventional crops even if no such differences exist in reality.

and

Yang, Y.T.; Chen, B. (2016). "Governing GMOs in the USA: science, law and public health". Journal of the Science of Food and Agriculture. 96: 18511855. doi:10.1002/jsfa.7523. PMID26536836. It is therefore not surprising that efforts to require labeling and to ban GMOs have been a growing political issue in the USA (citing Domingo and Bordonaba, 2011).

Overall, a broad scientific consensus holds that currently marketed GM food poses no greater risk than conventional food... Major national and international science and medical associations have stated that no adverse human health effects related to GMO food have been reported or substantiated in peer-reviewed literature to date.

Despite various concerns, today, the American Association for the Advancement of Science, the World Health Organization, and many independent international science organizations agree that GMOs are just as safe as other foods. Compared with conventional breeding techniques, genetic engineering is far more precise and, in most cases, less likely to create an unexpected outcome.

Pinholster, Ginger (October 25, 2012). "AAAS Board of Directors: Legally Mandating GM Food Labels Could "Mislead and Falsely Alarm Consumers"". American Association for the Advancement of Science. Retrieved February 8, 2016.

"REPORT 2 OF THE COUNCIL ON SCIENCE AND PUBLIC HEALTH (A-12): Labeling of Bioengineered Foods" (PDF). American Medical Association. 2012. Retrieved March 19, 2016. Bioengineered foods have been consumed for close to 20 years, and during that time, no overt consequences on human health have been reported and/or substantiated in the peer-reviewed literature.

GM foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved. Continuous application of safety assessments based on the Codex Alimentarius principles and, where appropriate, adequate post market monitoring, should form the basis for ensuring the safety of GM foods.

"Genetically modified foods and health: a second interim statement" (PDF). British Medical Association. March 2004. Retrieved March 21, 2016. In our view, the potential for GM foods to cause harmful health effects is very small and many of the concerns expressed apply with equal vigour to conventionally derived foods. However, safety concerns cannot, as yet, be dismissed completely on the basis of information currently available.

When seeking to optimise the balance between benefits and risks, it is prudent to err on the side of caution and, above all, learn from accumulating knowledge and experience. Any new technology such as genetic modification must be examined for possible benefits and risks to human health and the environment. As with all novel foods, safety assessments in relation to GM foods must be made on a case-by-case basis.

Members of the GM jury project were briefed on various aspects of genetic modification by a diverse group of acknowledged experts in the relevant subjects. The GM jury reached the conclusion that the sale of GM foods currently available should be halted and the moratorium on commercial growth of GM crops should be continued. These conclusions were based on the precautionary principle and lack of evidence of any benefit. The Jury expressed concern over the impact of GM crops on farming, the environment, food safety and other potential health effects.

The Royal Society review (2002) concluded that the risks to human health associated with the use of specific viral DNA sequences in GM plants are negligible, and while calling for caution in the introduction of potential allergens into food crops, stressed the absence of evidence that commercially available GM foods cause clinical allergic manifestations. The BMA shares the view that that there is no robust evidence to prove that GM foods are unsafe but we endorse the call for further research and surveillance to provide convincing evidence of safety and benefit.

See the original post:
Genetically modified food - Wikipedia

This article is about the human eye. For eyes in general, see Eye.

The human eye is an organ that reacts to light and has several purposes. As a sense organ, the mammalian eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth. The human eye can distinguish about 10 million colors[1] and is possibly capable of detecting a single photon.[2]

Similar to the eyes of other mammals, the human eye's non-image-forming photosensitive ganglion cells in the retina receive light signals which affect adjustment of the size of the pupil, regulation and suppression of the hormone melatonin and entrainment of the body clock.[3]

The eye is not shaped like a perfect sphere, rather it is a fused two-piece unit, composed of the anterior segment and the posterior segment. The anterior segment is made up of the cornea, iris and lens. The cornea is transparent and more curved, and is linked to the larger posterior segment, composed of the vitreous, retina, choroid and the outer white shell called the sclera. The cornea is typically about 11.5mm (0.3in) in diameter, and 1/2 mm (500 um) in thickness near its center. The posterior chamber constitutes the remaining five-sixths; its diameter is typically about 24mm. The cornea and sclera are connected by an area termed the limbus. The iris is the pigmented circular structure concentrically surrounding the center of the eye, the pupil, which appears to be black. The size of the pupil, which controls the amount of light entering the eye, is adjusted by the iris' dilator and sphincter muscles.

Light energy enters the eye through the cornea, through the pupil and then through the lens. The lens shape is changed for near focus (accommodation) and is controlled by the ciliary muscle. Photons of light falling on the light-sensitive cells of the retina (photoreceptor cones and rods) are converted into electrical signals that are transmitted to the brain by the optic nerve and interpreted as sight and vision.

Dimensions typically differ among adults by only one or two millimetres, remarkably consistent across different ethnicities. The vertical measure, generally less than the horizontal, is about 24mm. The transverse size of a human adult eye is approximately 24.2mm and the sagittal size is 23.7mm with no significant difference between sexes and age groups. Strong correlation has been found between the transverse diameter and the width of the orbit (r = 0.88).[4] The typical adult eye has an anterior to posterior diameter of 24 millimetres, a volume of six cubic centimetres (0.4 cu. in.),[5] and a mass of 7.5 grams (weight of 0.25 oz.).[citation needed]

The eyeball grows rapidly, increasing from about 1617 millimetres (about 0.65inch) at birth to 22.523mm (approx. 0.89 in) by three years of age. By age 13, the eye attains its full size.

The eye is made up of three coats, or layers, enclosing various anatomical structures. The outermost layer, known as the fibrous tunic, is composed of the cornea and sclera. The middle layer, known as the vascular tunic or uvea, consists of the choroid, ciliary body, pigmented epithelium and iris. The innermost is the retina, which gets its oxygenation from the blood vessels of the choroid (posteriorly) as well as the retinal vessels (anteriorly).

The spaces of the eye are filled with the aqueous humour anteriorly, between the cornea and lens, and the vitreous body, a jelly-like substance, behind the lens, filling the entire posterior cavity. The aqueous humour is a clear watery fluid that is contained in two areas: the anterior chamber between the cornea and the iris, and the posterior chamber between the iris and the lens. The lens is suspended to the ciliary body by the suspensory ligament (Zonule of Zinn), made up of hundreds of fine transparent fibers which transmit muscular forces to change the shape of the lens for accommodation (focusing). The vitreous body is a clear substance composed of water and proteins, which give it a jelly-like and sticky composition.[6]

The approximate field of view of an individual human eye (measured from the fixation point, i.e., the point at which one's gaze is directed) varies by facial anatomy, but is typically 30 superior (up, limited by the brow), 45 nasal (limited by the nose), 70 inferior (down), and 100 temporal (towards the temple).[7][8][9] For both eyes combined (binocular) visual field is 100 vertical and 200 horizontal.[10][11] When viewed at large angles from the side, the iris and pupil may still be visible by the viewer, indicating the person has peripheral vision possible at that angle.[12][13][14]

About 15 temporal and 1.5 below the horizontal is the blind spot created by the optic nerve nasally, which is roughly 7.5 high and 5.5 wide.[15]

The retina has a static contrast ratio of around 100 000:1 (about 6.5 f-stops). As soon as the eye moves rapidly to acquire a target (saccades), it re-adjusts its exposure by adjusting the iris, which adjusts the size of the pupil. Initial dark adaptation takes place in approximately four seconds of profound, uninterrupted darkness; full adaptation through adjustments in retinal rod photoreceptors is 80% complete in thirty minutes. The process is nonlinear and multifaceted, so an interruption by light exposure requires restarting the dark adaptation process over again. Full adaptation is dependent on good blood flow; thus dark adaptation may be hampered by retinal disease, poor vascular circulation and high altitude exposure.[citation needed]

The human eye can detect a luminance range of 1014, or one hundred trillion (100,000,000,000,000) (about 46.5 f-stops), from 106 cd/m2, or one millionth (0.000001) of a candela per square meter to 108 cd/m2 or one hundred million (100,000,000) candelas per square meter.[16][17][18] This range does not include looking at the midday sun (109 cd/m2)[19] or lightning discharge.

At the low end of the range is the absolute threshold of vision for a steady light across a wide field of view, about 106 cd/m2 (0.000001 candela per square meter).[20][21] The upper end of the range is given in terms of normal visual performance as 108 cd/m2 (100,000,000 or one hundred million candelas per square meter).[22]

The eye includes a lens similar to lenses found in optical instruments such as cameras and the same physics principles can be applied. The pupil of the human eye is its aperture; the iris is the diaphragm that serves as the aperture stop. Refraction in the cornea causes the effective aperture (the entrance pupil) to differ slightly from the physical pupil diameter. The entrance pupil is typically about 4mm in diameter, although it can range from 2mm (f/8.3) in a brightly lit place to 8mm (f/2.1) in the dark. The latter value decreases slowly with age; older people's eyes sometimes dilate to not more than 5-6mm in the dark, and may be as small as 1mm in the light.[23][24]

The visual system in the human brain is too slow to process information if images are slipping across the retina at more than a few degrees per second.[25] Thus, to be able to see while moving, the brain must compensate for the motion of the head by turning the eyes. Frontal-eyed animals have a small area of the retina with very high visual acuity, the fovea centralis. It covers about 2 degrees of visual angle in people. To get a clear view of the world, the brain must turn the eyes so that the image of the object of regard falls on the fovea. Any failure to make eye movements correctly can lead to serious visual degradation.

Having two eyes allows the brain to determine the depth and distance of an object, called stereovision, and gives the sense of three-dimensionality to the vision. Both eyes must point accurately enough that the object of regard falls on corresponding points of the two retinas to stimulate stereovison; otherwise, double vision might occur. Some persons with congenitally crossed eyes tend to ignore one eye's vision, thus do not suffer double vision, and do not have stereovision. The movements of the eye are controlled by six muscles attached to each eye. and allow the eye to elevate, depress, converge, diverge and roll. These muscles are both controlled voluntarily and involuntarily to track objects and correct for simultaneous head movements.

Each eye has six muscles that control its movements: the lateral rectus, the medial rectus, the inferior rectus, the superior rectus, the inferior oblique, and the superior oblique. When the muscles exert different tensions, a torque is exerted on the globe that causes it to turn, in almost pure rotation, with only about one millimeter of translation.[26] Thus, the eye can be considered as undergoing rotations about a single point in the center of the eye.

Rapid eye movement, REM, typically refers to the sleep stage during which the most vivid dreams occur. During this stage, the eyes move rapidly. It is not in itself a unique form of eye movement.

Saccades are quick, simultaneous movements of both eyes in the same direction controlled by the frontal lobe of the brain. Some irregular drifts, movements, smaller than a saccade and larger than a microsaccade, subtend up to one tenth of a degree.

Even when looking intently at a single spot, the eyes drift around. This ensures that individual photosensitive cells are continually stimulated in different degrees. Without changing input, these cells would otherwise stop generating output. Microsaccades move the eye no more than a total of 0.2 in adult humans.

The vestibulo-ocular reflex is a reflex eye movement that stabilizes images on the retina during head movement by producing an eye movement in the direction opposite to head movement in response to neural input from the vestibular system of the inner ear, thus maintaining the image in the center of the visual field. For example, when the head moves to the right, the eyes move to the left. This applies for head movements up and down, left and right, and tilt to the right and left, all of which give input to the ocular muscles to maintain visual stability.

Eyes can also follow a moving object around. This tracking is less accurate than the vestibulo-ocular reflex, as it requires the brain to process incoming visual information and supply feedback. Following an object moving at constant speed is relatively easy, though the eyes will often make saccadic jerks to keep up. The smooth pursuit movement can move the eye at up to 100/s in adult humans.

It is more difficult to visually estimate speed in low light conditions or while moving, unless there is another point of reference for determining speed.

The optokinetic reflex is a combination of a saccade and smooth pursuit movement. When, for example, looking out of the window at a moving train, the eyes can focus on a 'moving' train for a short moment (through smooth pursuit), until the train moves out of the field of vision. At this point, the optokinetic reflex kicks in, and moves the eye back to the point where it first saw the train (through a saccade).

The adjustment to close-range vision involves three processes to focus an image on the retina.

When a creature with binocular vision looks at an object, the eyes must rotate around a vertical axis so that the projection of the image is in the centre of the retina in both eyes. To look at a nearby object, the eyes rotate 'towards each other' (convergence), while for an object farther away they rotate 'away from each other' (divergence).

Lenses cannot refract light rays at their edges as well as they can closer to the center. The image produced by any lens is therefore somewhat blurry around the edges (spherical aberration). It can be minimized by screening out peripheral light rays and looking only at the better-focused center. In the eye, the pupil serves this purpose by constricting while the eye is focused on nearby objects. Small aperatures also give an increase in depth of field, allowing a broader range of "in focus" vision. In this way the pupil has a dual purpose for near vision: to reduce spherical aberration and increase depth of field.[27]

Changing the curvature of the lens is carried out by the ciliary muscles surrounding the lens; this process is called "accommodation". Accommodation narrows the inner diameter of the ciliary body, which actually relaxes the fibers of the suspensory ligament attached to the periphery of the lens, and allows the lens to relax into a more convex, or globular, shape. A more convex lens refracts light more strongly and focuses divergent light rays from near objects onto the retina, allowing closer objects to be brought into better focus.[27][28]

The human eye contains enough complexity to warrant specialized attention and care beyond the duties of a general practitioner. These specialists, or eye care professionals, serve different functions in different countries. Eye care professionals can have overlap in their patient care privileges: both an ophthalmologist (M.D.) and optometrist (D.O.) are professionals who diagnoses eye disease and can prescribe lenses to correct vision,; but, typically, the ophthalmologist is licensed to perform surgery and perform complex procedures to correct disease:

Eye irritation has been defined as the magnitude of any stinging, scratching, burning, or other irritating sensation from the eye.[29] It is a common problem experienced by people of all ages. Related eye symptoms and signs of irritation are discomfort, dryness, excess tearing, itching, grating, foreign body sensation, ocular fatigue, pain, scratchiness, soreness, redness, swollen eyelids, and tiredness, etc. These eye symptoms are reported with intensities from mild to severe. It has been suggested that these eye symptoms are related to different causal mechanisms, and symptoms are related to the particular ocular anatomy involved.[30]

Several suspected causal factors in our environment have been studied so far.[29] One hypothesis is that indoor air pollution may cause eye and airway irritation.[31][32] Eye irritation depends somewhat on destabilization of the outer-eye tear film, in which the formation of dry spots on the cornea, resulting in ocular discomfort.[31][33][34] Occupational factors are also likely to influence the perception of eye irritation. Some of these are lighting (glare and poor contrast), gaze position, reduced blink rate, limited number of breaks from visual tasking, and a constant combination of accommodation, musculoskeletal burden, and impairment of the visual nervous system.[35][36] Another factor that may be related is work stress.[37][38] In addition, psychological factors have been found in multivariate analyses to be associated with an increase in eye irritation among VDU users.[39][40] Other risk factors, such as chemical toxins/irritants (e.g. amines, formaldehyde, acetaldehyde, acrolein, N-decane, VOCs, ozone, pesticides and preservatives, allergens, etc.) might cause eye irritation as well.

Certain volatile organic compounds that are both chemically reactive and airway irritants may cause eye irritation. Personal factors (e.g. use of contact lenses, eye make-up, and certain medications) may also affect destabilization of the tear film and possibly result in more eye symptoms.[30] Nevertheless, if airborne particles alone should destabilize the tear film and cause eye irritation, their content of surface-active compounds must be high.[30] An integrated physiological risk model with blink frequency, destabilization, and break-up of the eye tear film as inseparable phenomena may explain eye irritation among office workers in terms of occupational, climate, and eye-related physiological risk factors.[30]

There are two major measures of eye irritation. One is blink frequency which can be observed by human behavior. The other measures are break up time, tear flow, hyperemia (redness, swelling), tear fluid cytology, and epithelial damage (vital stains) etc., which are human beings physiological reactions. Blink frequency is defined as the number of blinks per minute and it is associated with eye irritation. Blink frequencies are individual with mean frequencies of < 2-3 to 20-30 blinks/minute, and they depend on environmental factors including the use of contact lenses. Dehydration, mental activities, work conditions, room temperature, relative humidity, and illumination all influence blink frequency. Break-up time (BUT) is another major measure of eye irritation and tear film stability.[41] It is defined as the time interval (in seconds) between blinking and rupture. BUT is considered to reflect the stability of the tear film as well. In normal persons, the break-up time exceeds the interval between blinks, and, therefore, the tear film is maintained.[30] Studies have shown that blink frequency is correlated negatively with break-up time. This phenomenon indicates that perceived eye irritation is associated with an increase in blink frequency since the cornea and conjunctiva both have sensitive nerve endings that belong to the first trigeminal branch.[42][43] Other evaluating methods, such as hyperemia, cytology etc. have increasingly been used to assess eye irritation.

There are other factors that are related to eye irritation as well. Three major factors that influence the most are indoor air pollution, contact lenses and gender differences. Field studies have found that the prevalence of objective eye signs is often significantly altered among office workers in comparisons with random samples of the general population.[44][45][46][47] These research results might indicate that indoor air pollution has played an important role in causing eye irritation. There are more and more people wearing contact lens now and dry eyes appear to be the most common complaint among contact lens wearers.[48][49][50] Although both contact lens wearers and spectacle wearers experience similar eye irritation symptoms, dryness, redness, and grittiness have been reported far more frequently among contact lens wearers and with greater severity than among spectacle wearers.[50] Studies have shown that incidence of dry eyes increases with age.[51][52] especially among women.[53] Tear film stability (e.g. break-up time) is significantly lower among women than among men. In addition, women have a higher blink frequency while reading.[54] Several factors may contribute to gender differences. One is the use of eye make-up. Another reason could be that the women in the reported studies have done more VDU work than the men, including lower grade work. A third often-quoted explanation is related to the age-dependent decrease of tear secretion, particularly among women after 40 years of age.[53][55][56]

In a study conducted by UCLA, the frequency of reported symptoms in industrial buildings was investigated.[57] The study's results were that eye irritation was the most frequent symptom in industrial building spaces, at 81%. Modern office work with use of office equipment has raised concerns about possible adverse health effects.[58] Since the 1970s, reports have linked mucosal, skin, and general symptoms to work with self-copying paper. Emission of various particulate and volatile substances has been suggested as specific causes. These symptoms have been related to Sick building syndrome (SBS), which involves symptoms such as irritation to the eyes, skin, and upper airways, headache and fatigue.[59]

Many of the symptoms described in SBS and multiple chemical sensitivity (MCS) resemble the symptoms known to be elicited by airborne irritant chemicals.[60] A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts.[61] The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row.[61] Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure.[61]

Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust.[61]

Several actions can be taken to prevent eye irritation

In addition, other measures are proper lid hygiene, avoidance of eye rubbing,[69] and proper use of personal products and medication. Eye make-up should be used with care.[70]

The paraphilic practice of oculolinctus, or eyeball-licking, may also cause irritations, infections, or damage to the eye.[71]

There are many diseases, disorders, and age-related changes that may affect the eyes and surrounding structures.

As the eye ages, certain changes occur that can be attributed solely to the aging process. Most of these anatomic and physiologic processes follow a gradual decline. With aging, the quality of vision worsens due to reasons independent of diseases of the aging eye. While there are many changes of significance in the non-diseased eye, the most functionally important changes seem to be a reduction in pupil size and the loss of accommodation or focusing capability (presbyopia). The area of the pupil governs the amount of light that can reach the retina. The extent to which the pupil dilates decreases with age, leading to a substantial decrease in light received at the retina. In comparison to younger people, it is as though older persons are constantly wearing medium-density sunglasses. Therefore, for any detailed visually guided tasks on which performance varies with illumination, older persons require extra lighting. Certain ocular diseases can come from sexually transmitted diseases such as herpes and genital warts. If contact between the eye and area of infection occurs, the STD can be transmitted to the eye.[72]

With aging, a prominent white ring develops in the periphery of the cornea called arcus senilis. Aging causes laxity, downward shift of eyelid tissues and atrophy of the orbital fat. These changes contribute to the etiology of several eyelid disorders such as ectropion, entropion, dermatochalasis, and ptosis. The vitreous gel undergoes liquefaction (posterior vitreous detachment or PVD) and its opacities visible as floaters gradually increase in number.

Various eye care professionals, including ophthalmologists, optometrists, and opticians, are involved in the treatment and management of ocular and vision disorders. A Snellen chart is one type of eye chart used to measure visual acuity. At the conclusion of a complete eye examination, the eye doctor might provide the patient with an eyeglass prescription for corrective lenses. Some disorders of the eyes for which corrective lenses are prescribed include myopia (near-sightedness) which affects about one-third[citation needed] of the human population, hyperopia (far-sightedness) which affects about one quarter of the population, astigmatism, and presbyopia (the loss of focusing range during aging).

Macular degeneration is especially prevalent in the U.S. and affects roughly 1.75 million Americans each year.[73] Having lower levels of lutein and zeaxanthin within the macula may be associated with an increase in the risk of age-related macular degeneration,.[74][75] Lutein and zeaxanthin act as antioxidants that protect the retina and macula from oxidative damage from high-energy light waves.[76] As the light waves enter the eye they excite electrons that can cause harm to the cells in the eye, but before they can cause oxidative damage that may lead to macular degeneration or cataracts. Lutein and zeaxanthin bind to the electron free radical and are reduced rendering the electron safe. There are many ways to ensure a diet rich in lutein and zeaxanthin, the best of which is to eat dark green vegetables including kale, spinach, broccoli and turnip greens.[77] Nutrition is an important aspect of the ability to achieve and maintain proper eye health. Lutein and zeaxanthin are two major carotenoids, found in the macula of the eye, that are being researched to identify their role in the pathogenesis of eye disorders such as age-related macular degeneration and cataracts.[78]

Right eye without labels (horizontal section)

Eye and orbit anatomy with motor nerves

Image showing orbita with eye and nerves visible (periocular fat removed).

Image showing orbita with eye and periocular fat.

The structures of the eye labeled

Another view of the eye and the structures of the eye labeled

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Human eye - Wikipedia

Cloning is the process of creating a copy of a biological entity. In genetics, it refers to the process of making an identical copy of the DNA of an organism. Are you interested in understanding the pros and cons of cloning?

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When Dolly, the first cloned sheep came in the news, cloning interested the masses. Not only researchers but even common people became interested in knowing about how cloning is done and what pros and cons it has. Everyone became more curious about how cloning could benefit the common man. Most of us want to know the pros and cons of cloning, its advantages and its potential risks to mankind. Let us understand them.

Cloning finds applications in genetic fingerprinting, amplification of DNA and alteration of the genetic makeup of organisms. It can be used to bring about desired changes in the genetic makeup of individuals thereby introducing positive traits in them, as also for the elimination of negative traits. Cloning can also be applied to plants to remove or alter defective genes, thereby making them resistant to diseases. Cloning may find applications in the development of human organs, thus making human life safer. Here we look at some of the potential advantages of cloning.

Organ Replacement

If vital organs of the human body can be cloned, they can serve as backups. Cloning body parts can serve as a lifesaver. When a body organ such as a kidney or heart fails to function, it may be possible to replace it with the cloned body organ.

Substitute for Natural Reproduction

Cloning in human beings can prove to be a solution to infertility. It can serve as an option for producing children. With cloning, it would be possible to produce certain desired traits in human beings. We might be able to produce children with certain qualities. Wouldn't that be close to creating a man-made being?!

Help in Genetic Research

Cloning technologies can prove helpful to researchers in genetics. They might be able to understand the composition of genes and the effects of genetic constituents on human traits, in a better manner. They will be able to alter genetic constituents in cloned human beings, thus simplifying their analysis of genes. Cloning may also help us combat a wide range of genetic diseases.

Obtain Specific Traits in Organisms

Cloning can make it possible for us to obtain customized organisms and harness them for the benefit of society. It can serve as the best means to replicate animals that can be used for research purposes. It can enable the genetic alteration of plants and animals. If positive changes can be brought about in living beings with the help of cloning, it will indeed be a boon to mankind.

Like every coin has two sides, cloning has its flip side too. Though cloning may work wonders in genetics, it has some potential disadvantages. Cloning, as you know, is copying or replicating biological traits in organisms. Thus it might reduce the diversity in nature. Imagine multiple living entities like one another! Another con of cloning is that it is not clear whether we will be able to bring all the potential uses of cloning into reality. Plus, there's a big question of whether the common man will afford harnessing cloning technologies to his benefit. Here we look at the potential disadvantages of cloning.

Detrimental to Genetic Diversity

Cloning creates identical genes. It is a process of replicating a genetic constitution, thus hampering the diversity in genes. In lessening genetic diversity, we weaken our ability of adaptation. Cloning is also detrimental to the beauty that lies in diversity.

Invitation to Malpractices

While cloning allows man to tamper with genes in human beings, it also makes deliberate reproduction of undesirable traits, a possibility. Cloning of body organs may invite malpractices in society.

Will it Reach the Common Man?

In cloning human organs and using them for transplant, or in cloning human beings themselves, technical and economic barriers will have to be considered. Will cloned organs be cost-effective? Will cloning techniques really reach the common man?

Man, a Man-made Being?

Moreover, cloning will put human and animal rights at stake. Will cloning fit into our ethical and moral principles? It will make man just another man-made being. Won't it devalue mankind? Won't it demean the value of human life?

Cloning is equal to emulating God. Is that easy? Is it risk-free? Many are afraid it is not.

Manali Oak

Last Updated: August 8, 2016

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