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Genetic engineering

Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus.

As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome.

An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is a genetically modified organism (GMO). The first GMO was a bacterium generated by Herbert Boyer and Stanley Cohen in 1973. Rudolf Jaenisch created the first GM animal when he inserted foreign DNA into a mouse in 1974. The first company to focus on genetic engineering, Genentech, was founded in 1976 and started the production of human proteins. Genetically engineered human insulin was produced in 1978 and insulin-producing bacteria were commercialised in 1982. Genetically modified food has been sold since 1994, with the release of the Flavr Savr tomato. The Flavr Savr was engineered to have a longer shelf life, but most current GM crops are modified to increase resistance to insects and herbicides. GloFish, the first GMO designed as a pet, was sold in the United States in December 2003. In 2016 salmon modified with a growth hormone were sold.

Genetic engineering has been applied in numerous fields including research, medicine, industrial biotechnology and agriculture. In research, GMOs are used to study gene function and expression through loss of function, gain of function, tracking and expression experiments. By knocking out genes responsible for certain conditions it is possible to create animal model organisms of human diseases. As well as producing hormones, vaccines and other drugs, genetic engineering has the potential to cure genetic diseases through gene therapy. Chinese hamster ovary (CHO) cells are used in industrial genetic engineering. Additionally mRNA vaccines are made through genetic engineering to treat viruses such as COVID-19. The same techniques that are used to produce drugs can also have industrial applications such as producing enzymes for laundry detergent, cheeses and other products.

The rise of commercialised genetically modified crops has provided economic benefit to farmers in many different countries, but has also been the source of most of the controversy surrounding the technology. This has been present since its early use; the first field trials were destroyed by anti-GM activists. Although there is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, critics consider GM food safety a leading concern. Gene flow, impact on non-target organisms, control of the food supply and intellectual property rights have also been raised as potential issues. These concerns have led to the development of a regulatory framework, which started in 1975. It has led to an international treaty, the Cartagena Protocol on Biosafety, that was adopted in 2000. Individual countries have developed their own regulatory systems regarding GMOs, with the most marked differences occurring between the United States and Europe.

Overview

Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducing DNA, or modifying existing genetic material in situ. Unlike traditional animal and plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired phenotype, genetic engineering takes the gene directly from one organism and delivers it to the other. This is much faster, can be used to insert any genes from any organism (even ones from different domains) and prevents other undesirable genes from also being added.

Genetic engineering could potentially fix severe genetic disorders in humans by replacing the defective gene with a functioning one. It is an important tool in research that allows the function of specific genes to be studied. Drugs, vaccines and other products have been harvested from organisms engineered to produce them. Crops have been developed that aid food security by increasing yield, nutritional value and tolerance to environmental stresses.

The DNA can be introduced directly into the host organism or into a cell that is then fused or hybridised with the host. This relies on recombinant nucleic acid techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macro-injection or micro-encapsulation.

Genetic engineering does not normally include traditional breeding, in vitro fertilisation, induction of polyploidy, mutagenesis and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process. However, some broad definitions of genetic engineering include selective breeding. Cloning and stem cell research, although not considered genetic engineering, are closely related and genetic engineering can be used within them. Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesised material into an organism.

Plants, animals or microorganisms that have been changed through genetic engineering are termed genetically modified organisms or GMOs. If genetic material from another species is added to the host, the resulting organism is called transgenic. If genetic material from the same species or a species that can naturally breed with the host is used the resulting organism is called cisgenic. If genetic engineering is used to remove genetic material from the target organism the resulting organism is termed a knockout organism. In Europe genetic modification is synonymous with genetic engineering while within the United States of America and Canada genetic modification can also be used to refer to more conventional breeding methods.

History
Humans have altered the genomes of species for thousands of years through selective breeding, or artificial selection  as contrasted with natural selection. More recently, mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations, for selective breeding purposes. Genetic engineering as the direct manipulation of DNA by humans outside breeding and mutations has only existed since the 1970s. The term "genetic engineering" was coined by the Russian-born geneticist Nikolay Timofeev-Ressovsky in his 1934 paper "The Experimental Production of Mutations", published in the British journal Biological Reviews. Jack Williamson used the term in his science fiction novel Dragon's Island, published in 1951 – one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase, and two years before James Watson and Francis Crick showed that the DNA molecule has a double-helix structure – though the general concept of direct genetic manipulation was explored in rudimentary form in Stanley G. Weinbaum's 1936 science fiction story Proteus Island.

In 1972, Paul Berg created the first recombinant DNA molecules by combining DNA from the monkey virus SV40 with that of the lambda virus. In 1973 Herbert Boyer and Stanley Cohen created the first transgenic organism by inserting antibiotic resistance genes into the plasmid of an Escherichia coli bacterium. A year later Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal These achievements led to concerns in the scientific community about potential risks from genetic engineering, which were first discussed in depth at the Asilomar Conference in 1975. One of the main recommendations from this meeting was that government oversight of recombinant DNA research should be established until the technology was deemed safe.

In 1976 Genentech, the first genetic engineering company, was founded by Herbert Boyer and Robert Swanson and a year later the company produced a human protein (somatostatin) in E. coli. Genentech announced the production of genetically engineered human insulin in 1978. In 1980, the U.S. Supreme Court in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented. The insulin produced by bacteria was approved for release by the Food and Drug Administration (FDA) in 1982.

In 1983, a biotech company, Advanced Genetic Sciences (AGS) applied for U.S. government authorisation to perform field tests with the ice-minus strain of Pseudomonas syringae to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges. In 1987, the ice-minus strain of P. syringae became the first genetically modified organism (GMO) to be released into the environment when a strawberry field and a potato field in California were sprayed with it. Both test fields were attacked by activist groups the night before the tests occurred: "The world's first trial site attracted the world's first field trasher".

The first field trials of genetically engineered plants occurred in France and the US in 1986, tobacco plants were engineered to be resistant to herbicides. The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992. In 1994 Calgene attained approval to commercially release the first genetically modified food, the Flavr Savr, a tomato engineered to have a longer shelf life. In 1994, the European Union approved tobacco engineered to be resistant to the herbicide bromoxynil, making it the first genetically engineered crop commercialised in Europe. In 1995, Bt potato was approved safe by the Environmental Protection Agency, after having been approved by the FDA, making it the first pesticide producing crop to be approved in the US. In 2009 11 transgenic crops were grown commercially in 25 countries, the largest of which by area grown were the US, Brazil, Argentina, India, Canada, China, Paraguay and South Africa.

In 2010, scientists at the J. Craig Venter Institute created the first synthetic genome and inserted it into an empty bacterial cell. The resulting bacterium, named Mycoplasma laboratorium, could replicate and produce proteins. Four years later this was taken a step further when a bacterium was developed that replicated a plasmid containing a unique base pair, creating the first organism engineered to use an expanded genetic alphabet. In 2012, Jennifer Doudna and Emmanuelle Charpentier collaborated to develop the CRISPR/Cas9 system, a technique which can be used to easily and specifically alter the genome of almost any organism.

Process
Creating a GMO is a multi-step process. Genetic engineers must first choose what gene they wish to insert into the organism. This is driven by what the aim is for the resultant organism and is built on earlier research. Genetic screens can be carried out to determine potential genes and further tests then used to identify the best candidates. The development of microarrays, transcriptomics and genome sequencing has made it much easier to find suitable genes. Luck also plays its part; the Roundup Ready gene was discovered after scientists noticed a bacterium thriving in the presence of the herbicide.

Gene isolation and cloning
The next step is to isolate the candidate gene. The cell containing the gene is opened and the DNA is purified. The gene is separated by using restriction enzymes to cut the DNA into fragments or polymerase chain reaction (PCR) to amplify up the gene segment. These segments can then be extracted through gel electrophoresis. If the chosen gene or the donor organism's genome has been well studied it may already be accessible from a genetic library. If the DNA sequence is known, but no copies of the gene are available, it can also be artificially synthesised. Once isolated the gene is ligated into a plasmid that is then inserted into a bacterium. The plasmid is replicated when the bacteria divide, ensuring unlimited copies of the gene are available. The RK2 plasmid is notable for its ability to replicate in a wide variety of single-celled organisms, which makes it suitable as a genetic engineering tool.

Before the gene is inserted into the target organism it must be combined with other genetic elements. These include a promoter and terminator region, which initiate and end transcription. A selectable marker gene is added, which in most cases confers antibiotic resistance, so researchers can easily determine which cells have been successfully transformed. The gene can also be modified at this stage for better expression or effectiveness. These manipulations are carried out using recombinant DNA techniques, such as restriction digests, ligations and molecular cloning.

Inserting DNA into the host genome
There are a number of techniques used to insert genetic material into the host genome. Some bacteria can naturally take up foreign DNA. This ability can be induced in other bacteria via stress (e.g. thermal or electric shock), which increases the cell membrane's permeability to DNA; up-taken DNA can either integrate with the genome or exist as extrachromosomal DNA. DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus, or through the use of viral vectors.

Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. In plants the DNA is often inserted using Agrobacterium-mediated transformation, taking advantage of the Agrobacteriums T-DNA sequence that allows natural insertion of genetic material into plant cells. Other methods include biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells, and electroporation, which involves using an electric shock to make the cell membrane permeable to plasmid DNA.

As only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through the use of tissue culture. In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells. Bacteria consist of a single cell and reproduce clonally so regeneration is not necessary. Selectable markers are used to easily differentiate transformed from untransformed cells. These markers are usually present in the transgenic organism, although a number of strategies have been developed that can remove the selectable marker from the mature transgenic plant.

Further testing using PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene. These tests can also confirm the chromosomal location and copy number of the inserted gene. The presence of the gene does not guarantee it will be expressed at appropriate levels in the target tissue so methods that look for and measure the gene products (RNA and protein) are also used. These include northern hybridisation, quantitative RT-PCR, Western blot, immunofluorescence, ELISA and phenotypic analysis.

The new genetic material can be inserted randomly within the host genome or targeted to a specific location. The technique of gene targeting uses homologous recombination to make desired changes to a specific endogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use of selectable markers. The frequency of gene targeting can be greatly enhanced through genome editing. Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome, and use the cell's endogenous mechanisms to repair the induced break by the natural processes of homologous recombination and nonhomologous end-joining. There are four families of engineered nucleases: meganucleases, zinc finger nucleases,  transcription activator-like effector nucleases (TALENs),  and the Cas9-guideRNA system (adapted from CRISPR). TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient. In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate a gene knockout.

Applications
Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and microorganisms. Bacteria, the first organisms to be genetically modified, can have plasmid DNA inserted containing new genes that code for medicines or enzymes that process food and other substrates. Plants have been modified for insect protection, herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of edible vaccines. Most commercialised GMOs are insect resistant or herbicide tolerant crop plants. Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. The genetically modified animals include animals with genes knocked out, increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk.

Medicine
Genetic engineering has many applications to medicine that include the manufacturing of drugs, creation of model animals that mimic human conditions and gene therapy. One of the earliest uses of genetic engineering was to mass-produce human insulin in bacteria. This application has now been applied to human growth hormones, follicle stimulating hormones (for treating infertility), human albumin, monoclonal antibodies, antihemophilic factors, vaccines and many other drugs. Mouse hybridomas, cells fused together to create monoclonal antibodies, have been adapted through genetic engineering to create human monoclonal antibodies. Genetically engineered viruses are being developed that can still confer immunity, but lack the infectious sequences.

Genetic engineering is also used to create animal models of human diseases. Genetically modified mice are the most common genetically engineered animal model. They have been used to study and model cancer (the oncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. Potential cures can be tested against these mouse models.

Gene therapy is the genetic engineering of humans, generally by replacing defective genes with effective ones. Clinical research using somatic gene therapy has been conducted with several diseases, including X-linked SCID, chronic lymphocytic leukemia (CLL), and Parkinson's disease. In 2012, Alipogene tiparvovec became the first gene therapy treatment to be approved for clinical use. In 2015 a virus was used to insert a healthy gene into the skin cells of a boy suffering from a rare skin disease, epidermolysis bullosa, in order to grow, and then graft healthy skin onto 80 percent of the boy's body which was affected by the illness.

Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community. In 2015, CRISPR was used to edit the DNA of non-viable human embryos, leading scientists of major world academies to call for a moratorium on inheritable human genome edits. There are also concerns that the technology could be used not just for treatment, but for enhancement, modification or alteration of a human beings' appearance, adaptability, intelligence, character or behavior. The distinction between cure and enhancement can also be difficult to establish. In November 2018, He Jiankui announced that he had edited the genomes of two human embryos, to attempt to disable the CCR5 gene, which codes for a receptor that HIV uses to enter cells. The work was widely condemned as unethical, dangerous, and premature. Currently, germline modification is banned in 40 countries. Scientists that do this type of research will often let embryos grow for a few days without allowing it to develop into a baby.

Researchers are altering the genome of pigs to induce the growth of human organs, with the aim of increasing the success of pig to human organ transplantation. Scientists are creating "gene drives", changing the genomes of mosquitoes to make them immune to malaria, and then looking to spread the genetically altered mosquitoes throughout the mosquito population in the hopes of eliminating the disease.

Research

Genetic engineering is an important tool for natural scientists, with the creation of transgenic organisms one of the most important tools for analysis of gene function. Genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research.

Organisms are genetically engineered to discover the functions of certain genes. This could be the effect on the phenotype of the organism, where the gene is expressed or what other genes it interacts with. These experiments generally involve loss of function, gain of function, tracking and expression.

 * Loss of function experiments, such as in a gene knockout experiment, in which an organism is engineered to lack the activity of one or more genes. In a simple knockout a copy of the desired gene has been altered to make it non-functional. Embryonic stem cells incorporate the altered gene, which replaces the already present functional copy. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. This allows the experimenter to analyse the defects caused by this mutation and thereby determine the role of particular genes. It is used especially frequently in developmental biology. When this is done by creating a library of genes with point mutations at every position in the area of interest, or even every position in the whole gene, this is called "scanning mutagenesis". The simplest method, and the first to be used, is "alanine scanning", where every position in turn is mutated to the unreactive amino acid alanine.
 * Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently. Gain of function is used to tell whether or not a protein is sufficient for a function, but does not always mean it is required, especially when dealing with genetic or functional redundancy.
 * Tracking experiments, which seek to gain information about the localisation and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as green fluorescent protein (GFP) that will allow easy visualisation of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences that will serve as binding motifs to monoclonal antibodies.
 * Expression studies aim to discover where and when specific proteins are produced. In these experiments, the DNA sequence before the DNA that codes for a protein, known as a gene's promoter, is reintroduced into an organism with the protein coding region replaced by a reporter gene such as GFP or an enzyme that catalyses the production of a dye. Thus the time and place where a particular protein is produced can be observed. Expression studies can be taken a step further by altering the promoter to find which pieces are crucial for the proper expression of the gene and are actually bound by transcription factor proteins; this process is known as promoter bashing.

Industrial
Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they will overexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism in bioreactor equipment using industrial fermentation, and then purifying the protein. Some genes do not work well in bacteria, so yeast, insect cells or mammalian cells can also be used. These techniques are used to produce medicines such as insulin, human growth hormone, and vaccines, supplements such as tryptophan, aid in the production of food (chymosin in cheese making) and fuels. Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as making biofuels, cleaning up oil spills, carbon and other toxic waste and detecting arsenic in drinking water. Certain genetically modified microbes can also be used in biomining and bioremediation, due to their ability to extract heavy metals from their environment and incorporate them into compounds that are more easily recoverable.

In materials science, a genetically modified virus has been used in a research laboratory as a scaffold for assembling a more environmentally friendly lithium-ion battery. Bacteria have also been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions.

Agriculture

One of the best-known and controversial applications of genetic engineering is the creation and use of genetically modified crops or genetically modified livestock to produce genetically modified food. Crops have been developed to increase production, increase tolerance to abiotic stresses, alter the composition of the food, or to produce novel products.

The first crops to be released commercially on a large scale provided protection from insect pests or tolerance to herbicides. Fungal and virus resistant crops have also been developed or are in development. This makes the insect and weed management of crops easier and can indirectly increase crop yield. GM crops that directly improve yield by accelerating growth or making the plant more hardy (by improving salt, cold or drought tolerance) are also under development. In 2016 Salmon have been genetically modified with growth hormones to reach normal adult size much faster.

GMOs have been developed that modify the quality of produce by increasing the nutritional value or providing more industrially useful qualities or quantities. The Amflora potato produces a more industrially useful blend of starches. Soybeans and canola have been genetically modified to produce more healthy oils. The first commercialised GM food was a tomato that had delayed ripening, increasing its shelf life.

Plants and animals have been engineered to produce materials they do not normally make. Pharming uses crops and animals as bioreactors to produce vaccines, drug intermediates, or the drugs themselves; the useful product is purified from the harvest and then used in the standard pharmaceutical production process. Cows and goats have been engineered to express drugs and other proteins in their milk, and in 2009 the FDA approved a drug produced in goat milk.

Other applications
Genetic engineering has potential applications in conservation and natural area management. Gene transfer through viral vectors has been proposed as a means of controlling invasive species as well as vaccinating threatened fauna from disease. Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations. With the increasing risks of maladaptation in organisms as a result of climate change and other perturbations, facilitated adaptation through gene tweaking could be one solution to reducing extinction risks. Applications of genetic engineering in conservation are thus far mostly theoretical and have yet to be put into practice.

Genetic engineering is also being used to create microbial art. Some bacteria have been genetically engineered to create black and white photographs. Novelty items such as lavender-colored carnations, blue roses, and glowing fish have also been produced through genetic engineering.

Regulation
The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of GMOs. The development of a regulatory framework began in 1975, at Asilomar, California. The Asilomar meeting recommended a set of voluntary guidelines regarding the use of recombinant technology. As the technology improved the US established a committee at the Office of Science and Technology, which assigned regulatory approval of GM food to the USDA, FDA and EPA. The Cartagena Protocol on Biosafety, an international treaty that governs the transfer, handling, and use of GMOs, was adopted on 29 January 2000. One hundred and fifty-seven countries are members of the Protocol, and many use it as a reference point for their own regulations.

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. Some countries allow the import of GM food with authorisation, but either do not allow its cultivation (Russia, Norway, Israel) or have provisions for cultivation even though no GM products are yet produced (Japan, South Korea). Most countries that do not allow GMO cultivation do permit research. Some of the most marked differences occur between the US and Europe. The US policy focuses on the product (not the process), only looks at verifiable scientific risks and uses the concept of substantial equivalence. The European Union by contrast has possibly the most stringent GMO regulations in the world. All GMOs, along with irradiated food, are considered "new food" and subject to extensive, case-by-case, science-based food evaluation by the European Food Safety Authority. The criteria for authorisation fall in four broad categories: "safety", "freedom of choice", "labelling", and "traceability". The level of regulation in other countries that cultivate GMOs lie in between Europe and the United States.

One of the key issues concerning regulators is whether GM products should be labeled. The European Commission says that mandatory labeling and traceability are needed to allow for informed choice, avoid potential false advertising and facilitate the withdrawal of products if adverse effects on health or the environment are discovered. The American Medical Association and the American Association for the Advancement of Science say that absent scientific evidence of harm even voluntary labeling is misleading and will falsely alarm consumers. Labeling of GMO products in the marketplace is required in 64 countries. Labeling can be mandatory up to a threshold GM content level (which varies between countries) or voluntary. In Canada and the US labeling of GM food is voluntary, while in Europe all food (including processed food) or feed which contains greater than 0.9% of approved GMOs must be labelled.

Controversy
Critics have objected to the use of genetic engineering on several grounds, including ethical, ecological and economic concerns. Many of these concerns involve GM crops and whether food produced from them is safe and what impact growing them will have on the environment. These controversies have led to litigation, international trade disputes, and protests, and to restrictive regulation of commercial products in some countries.

Accusations that scientists are "playing God" and other religious issues have been ascribed to the technology from the beginning. Other ethical issues raised include the patenting of life, the use of intellectual property rights, the level of labeling on products, control of the food supply and the objectivity of the regulatory process. Although doubts have been raised, economically most studies have found growing GM crops to be beneficial to farmers.

Gene flow between GM crops and compatible plants, along with increased use of selective herbicides, can increase the risk of "superweeds" developing. Other environmental concerns involve potential impacts on non-target organisms, including soil microbes, and an increase in secondary and resistant insect pests. Many of the environmental impacts regarding GM crops may take many years to be understood and are also evident in conventional agriculture practices. With the commercialisation of genetically modified fish there are concerns over what the environmental consequences will be if they escape.

There are three main concerns over the safety of genetically modified food: whether they may provoke an allergic reaction; whether the genes could transfer from the food into human cells; and whether the genes not approved for human consumption could outcross to other crops. There is a scientific consensus  But see also:

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that currently available food derived from GM crops poses no greater risk to human health than conventional food,    but that each GM food needs to be tested on a case-by-case basis before introduction. Some medical organizations, including the British Medical Association, advocate further caution based upon the precautionary principle: Nonetheless, members of the public are less likely than scientists to perceive GM foods as safe.

In popular culture
Genetic engineering features in many science fiction stories. Frank Herbert's novel The White Plague describes the deliberate use of genetic engineering to create a pathogen which specifically kills women. Another of Herbert's creations, the Dune series of novels, uses genetic engineering to create the powerful Tleilaxu. Few films have informed audiences about genetic engineering, with the exception of the 1978 The Boys from Brazil and the 1993 Jurassic Park, both of which make use of a lesson, a demonstration, and a clip of scientific film. Genetic engineering methods are weakly represented in film; Michael Clark, writing for the Wellcome Trust, calls the portrayal of genetic engineering and biotechnology "seriously distorted" in films such as The 6th Day. In Clark's view, the biotechnology is typically "given fantastic but visually arresting forms" while the science is either relegated to the background or fictionalised to suit a young audience.

title: Genetic engineering


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Gettysburg Address

The Gettysburg Address is a speech that U.S. President Abraham Lincoln delivered during the American Civil War at the dedication of the Soldiers' National Cemetery, now known as Gettysburg National Cemetery, in Gettysburg, Pennsylvania on the afternoon of November 19, 1863, four and a half months after the Union armies defeated Confederate forces in the Battle of Gettysburg, the Civil War's deadliest battle. The speech is widely considered one of the most notable and famous delivered in American history.

Lincoln's carefully crafted and brief address, which was not scheduled as the day's primary speech, came to be seen as one of the greatest and most influential statements on the American national purpose. In just 271 words, beginning with the now famous phrase "Four score and seven years ago", referring to the signing of the Declaration of Independence 87 years earlier, Lincoln described the U.S. as a nation "conceived in Liberty, and dedicated to the proposition that all men are created equal" and represented the Civil War as a test that would determine whether such a nation could endure. Lincoln extolled the sacrifices of those who died at Gettysburg in defense of those principles and then urged that the nation ensure:

"[...] that these dead shall not have died in vain—that this nation, under God, shall have a new birth of freedom —and that government of the people, by the people, for the people, shall not perish from the earth."

Despite the prominent place of the speech in the history and popular culture of the United States, its exact wording is disputed. The five known manuscripts of the Gettysburg Address in Lincoln's hand differ in a number of details, and also differ from contemporary newspaper reprints of the speech. Nor is it precisely clear where on the grounds of the Gettysburg cemetery Lincoln delivered the address. Modern scholarship locates the speakers' platform at least 120 ft away from the traditional site in Soldiers' National Cemetery at the Soldiers' National Monument, such that it stood entirely within the private adjacent Evergreen Cemetery. A 2022 interpretation of photographs of the day, using 3D modeling software, has argued for a slightly different locationstraddling the current fence around Evergreen Cemetery.

Background
Following the Battle of Gettysburg on July 1–3, 1863, the removal of the fallen Union soldiers from the Gettysburg Battlefield graves and their reburial in graves at the National Cemetery at Gettysburg began on October 17, though on the day of the ceremony, interment was less than half complete.

In inviting President Lincoln to the ceremonies, David Wills, of the committee for the November 19 Consecration of the National Cemetery at Gettysburg, wrote, "It is the desire that, after the Oration, you, as Chief Executive of the nation, formally set apart these grounds to their sacred use by a few appropriate remarks."

On the train trip from Washington, D.C. to Gettysburg on November 18, Lincoln was accompanied by three members of his Cabinet, William Seward, John Usher, and Montgomery Blair, several foreign officials, his secretary John Nicolay, and his assistant secretary, John Hay. During the trip, Lincoln remarked to Hay that he felt weak; on the morning of November 19, Lincoln mentioned to Nicolay that he was dizzy. Hay noted during the speech that Lincoln's face had "a ghastly color" and that he was "sad, mournful, almost haggard". After the speech, when Lincoln boarded the 6:30pm train to return to Washington, D.C., he was feverish and weak with a severe headache. A protracted illness followed, which included a vesicular rash; it was diagnosed as a mild case of smallpox. It is highly likely that Lincoln was in the prodromal period of smallpox as he delivered the Gettysburg Address.

After arriving in Gettysburg, which had become filled with large crowds, Lincoln spent the night in Wills's house. A large crowd appeared at the house, singing and wanting Lincoln to make a speech. Lincoln met the crowd but did not have a speech prepared, and he returned inside after saying a few extemporaneous words. The crowd then continued to another house where Secretary of State William Seward delivered a speech. Later that night, Lincoln wrote and briefly met with Seward before going to bed at about midnight.

Program and Everett's "Gettysburg Oration"
The program organized for that day by Wills and his committee included:

"Music, by Birgfeld's Band ('Homage d'uns Heros' by Adolph Birgfeld) Prayer, by Reverend T. H. Stockton, D.D.

The Marine Band ('Old Hundred'), directed by Francis Scala, provided music at the dedication.

Oration, by Hon. Edward Everett ('The Battles of Gettysburg')

Music, Hymn ('Consecration Chant') by B. B. French, Esq., music by Wilson G Horner, sung by Baltimore Glee Club

Dedicatory Remarks, by the President of the United States

Dirge ('Oh! It is Great for Our Country to Die', words by James G. Percival, music by Alfred Delaney), sung by Choir selected for the occasion

Benediction, by Reverend H. L. Baugher, D.D."

While it is Lincoln's short speech that has gone down in history as one of the finest examples of English public oratory, it was Everett's oration that was slated to be the "Gettysburg address" that day. His now seldom-read oration was 13,607 words long and lasted two hours.

Lengthy dedication addresses like Everett's were common at cemeteries in this era. The tradition began in 1831 when Justice Joseph Story delivered the dedication address at Mount Auburn Cemetery in Cambridge, Massachusetts. Those addresses often linked cemeteries to the mission of Union.

Text
Shortly after Everett's well-received remarks, Lincoln spoke for only a few minutes. His speech was ten sentences long.

Despite the historical significance of Lincoln's speech, modern scholars disagree as to its exact wording, and contemporary transcriptions published in newspaper accounts of the event and even handwritten copies by Lincoln himself differ in their wording, punctuation, and structure. Of these versions, the Bliss version, written well after the speech as a favor for a friend, is viewed by many as the standard text. Its text differs, however, from the written versions prepared by Lincoln before and after his speech. It is the only version to which Lincoln affixed his signature, and the last he is known to have written. The Bliss version is as follows:

Lincoln's sources
In Lincoln at Gettysburg, Garry Wills notes the parallels between Lincoln's speech and Pericles's Funeral Oration during the Peloponnesian War as described by Thucydides. Pericles' speech, like Lincoln's:

 * Begins with an acknowledgment of revered predecessors: "I shall begin with our ancestors: it is both just and proper that they should have the honor of the first mention on an occasion like the present"
 * Praises the uniqueness of the State's commitment to democracy: "If we look to the laws, they afford equal justice to all in their private differences"
 * Honors the sacrifice of the slain, "Thus choosing to die resisting, rather than to live submitting, they fled only from dishonor, but met danger face to face"
 * Exhorts the living to continue the struggle: "You, their survivors, must determine to have as unfaltering a resolution in the field, though you may pray that it may have a happier issue."

James M. McPherson notes this connection in his review of Wills's book. Gore Vidal also draws attention to this link in a BBC documentary about oration.

In contrast, writer Adam Gopnik, in The New Yorker, notes that while Everett's Oration was explicitly neoclassical, referring directly to Marathon and Pericles, "Lincoln's rhetoric is, instead, deliberately Biblical. (It is difficult to find a single obviously classical reference in any of his speeches.) Lincoln had mastered the sound of the King James Bible so completely that he could recast abstract issues of constitutional law in Biblical terms, making the proposition that Texas and New Hampshire should be forever bound by a single post office sound like something right out of Genesis."

Wills also observed Lincoln's usage of the imagery of birth, life, and death in reference to a nation "brought forth", "conceived", and that shall not "perish". A 1959 thesis by William J. Wolf suggested that the address had a central image of baptism, although Glenn LaFantasie, writing for the Journal of the Abraham Lincoln Association, believes that Wolf's position was likely an overstatement. Philip B. Kunhardt Jr. suggests that Lincoln was inspired by the Book of Common Prayer.

Allen C. Guelzo, the director of Civil War Era studies at Gettysburg College in Pennsylvania, and others have suggested that Lincoln's formulation "four score and seven" was an allusion to the King James Version of the Bible's, in which man's lifespan is given as "threescore years and ten; and if by reason of strength they be fourscore years". LaFantasie also connected "four score and seven years" with Psalms 90:10, and referred to Lincoln's usage of the phrase "our fathers" as "mindful of the Lord's Prayer". He also refers to Garry Wills's tracing of spiritual language in the address to the Gospel of Luke.

"Government of the people, by the people, for the people"
Several theories have been advanced by Lincoln scholars to explain the provenance of Lincoln's famous phrase "government of the people, by the people, for the people". Despite many claims, there is no evidence that a similar phrase appears in the Prologue to John Wycliffe's 1384 English translation of the Bible.

In a discussion "A more probable origin of a famous Lincoln phrase", in a letter to The American Monthly Review of Reviews, Unitarian minister John White Chadwick points to William Herndon, Lincoln's law partner, who wrote in the 1888 work Abraham Lincoln: The True Story of A Great Life that he had brought to Lincoln some of the sermons of abolitionist minister Theodore Parker, of Massachusetts, and that Lincoln was moved by Parker's use of this idea:

"I brought with me additional sermons and lectures of Theodore Parker, who was warm in his commendation of Lincoln. One of these was a lecture on 'The Effect of Slavery on the American People' ... which I gave to Lincoln, who read and returned it. He liked especially the following expression, which he marked with a pencil, and which he in substance afterwards used in his Gettysburg Address: 'Democracy is direct self-government, over all the people, for all the people, by all the people.'"

Craig R. Smith, in "Criticism of Political Rhetoric and Disciplinary Integrity", suggested Lincoln's view of the government as expressed in the Gettysburg Address was influenced by the noted speech of Massachusetts Senator Daniel Webster, the "Second Reply to Hayne", in which Webster famously thundered "Liberty and Union, now and forever, one and inseparable!" Specifically, in this speech on January 26, 1830, before the United States Senate, Webster described the federal government as: "made for the people, made by the people, and answerable to the people", foreshadowing Lincoln's "government of the people, by the people, for the people". Webster also noted, "This government, Sir, is the independent offspring of the popular will. It is not the creature of State legislatures; nay, more, if the whole truth must be told, the people brought it into existence, established it, and have hitherto supported it, for the very purpose, amongst others, of imposing certain salutary restraints on State sovereignties."

It is theorized, that Hungarian statesman Lajos Kossuth's February 19th, 1852 speech given at the Ohio State Legislature, might have also had an influence on Lincoln: "The spirit of our age is Democracy. All for the people, and all by the people. Nothing about the people without the people – That is Democracy! […]"

Five manuscripts
Each of the five known manuscript copies of the Gettysburg Address is named for the person who received it from Lincoln. Lincoln gave copies to his private secretaries, John Nicolay and John Hay. Both of these drafts were written around the time of his November 19 address, while the other three copies of the address, the Everett, Bancroft, and Bliss copies, were written by Lincoln for charitable purposes well after November 19. In part because Lincoln provided a title and signed and dated the Bliss copy, it has become the standard text of Lincoln's Gettysburg Address.

Nicolay and Hay were appointed custodians of Lincoln's papers by Lincoln's son Robert Todd Lincoln in 1874. After appearing in facsimile in an article written by John Nicolay in 1894, the Nicolay copy was presumably among the papers passed to Hay by Nicolay's daughter Helen upon Nicolay's death in 1901. Robert Lincoln began a search for the original copy in 1908, which resulted in the discovery of a handwritten copy of the Gettysburg Address among the bound papers of John Hay—a copy now known as the "Hay copy" or "Hay draft".

The Hay draft differed from the version of the Gettysburg Address published by John Nicolay in 1894 in a number of significant ways: it was written on a different type of paper, had a different number of words per line and number of lines, and contained editorial revisions in Lincoln's hand.

Both the Hay and Nicolay copies of the Address are within the Library of Congress, encased in specially designed, temperature-controlled, sealed containers with argon gas in order to protect the documents from oxidation and continued deterioration.

Nicolay copy
The Nicolay copy is often called the "first draft" because it is believed to be the earliest copy that exists. Scholars disagree over whether the Nicolay copy was actually the reading copy Lincoln held at Gettysburg on November 19. In an 1894 article that included a facsimile of this copy, Nicolay, who had become the custodian of Lincoln's papers, wrote that Lincoln had brought to Gettysburg the first part of the speech written in ink on Executive Mansion stationery, and that he had written the second page in pencil on lined paper before the dedication on November 19. Matching folds are still evident on the two pages, suggesting it could be the copy that eyewitnesses say Lincoln took from his coat pocket and read at the ceremony. Others believe that the delivery text has been lost, because some of the words and phrases of the Nicolay copy do not match contemporary transcriptions of Lincoln's original speech. The words "under God", for example, are missing in this copy from the phrase "that this nation shall have a new birth of freedom ..." In order for the Nicolay draft to have been the reading copy, either the contemporary transcriptions were inaccurate, or Lincoln would have had to depart from his written text in several instances. This copy of the Gettysburg Address apparently remained in John Nicolay's possession until his death in 1901, when it passed to his friend and colleague John Hay. It used to be on display as part of the American Treasures exhibition of the Library of Congress in Washington, D.C.

Hay copy
The existence of the Hay copy was first announced to the public in 1906, after the search for the "original manuscript" of the Address among the papers of John Hay brought it to light. Significantly, it differs somewhat from the manuscript of the Address described by John Nicolay in his article, and contains numerous omissions and inserts in Lincoln's own hand, including omissions critical to the basic meaning of the sentence, not simply words that would be added by Lincoln to strengthen or clarify their meaning. In this copy, as in the Nicolay copy, the words "under God" are not present.

This version has been described as "the most inexplicable" of the drafts and is sometimes referred to as the "second draft". The "Hay copy" was made either on the morning of the delivery of the Address, or shortly after Lincoln's return to Washington. Those who believe that it was completed on the morning of his address point to the fact that it contains certain phrases that are not in the first draft but are in the reports of the address as delivered and in subsequent copies made by Lincoln. It is probable, they conclude, that, as stated in the explanatory note accompanying the original copies of the first and second drafts in the Library of Congress, Lincoln held this second draft when he delivered the address. Lincoln eventually gave this copy to Hay, whose descendants donated both it and the Nicolay copy to the Library of Congress in 1916.

Everett copy
The Everett copy, also known as the "Everett-Keyes copy", was sent by President Lincoln to Edward Everett in early 1864, at Everett's request. Everett was collecting the speeches at the Gettysburg dedication into one bound volume to sell for the benefit of stricken soldiers at New York's Sanitary Commission Fair. The draft Lincoln sent became the third autograph copy, and is now in the possession of the Illinois State Historical Library in Springfield, Illinois, where it is displayed in the Treasures Gallery of the Abraham Lincoln Presidential Library and Museum.

Bancroft copy
The Bancroft copy of the Gettysburg Address was written out by President Lincoln in February 1864 at the request of George Bancroft, the famed historian and former Secretary of the Navy, whose comprehensive ten-volume History of the United States later led him to be known as the "father of American History". Bancroft planned to include this copy in Autograph Leaves of Our Country's Authors, which he planned to sell at a Soldiers' and Sailors' Sanitary Fair in Baltimore. As this fourth copy was written on both sides of the paper, it proved unusable for this purpose, and Bancroft was allowed to keep it. This manuscript is the only one accompanied both by a letter from Lincoln transmitting the manuscript and by the original envelope addressed and franked by Lincoln. This copy remained in the Bancroft family for many years, was sold to various dealers and purchased by Nicholas and Marguerite Lilly Noyes, who donated the manuscript to Cornell University in 1949. It is now held by the Division of Rare and Manuscript Collections in the Carl A. Kroch Library at Cornell. It is the only one of the five copies to be privately owned.

Bliss copy
Discovering that his fourth written copy could not be used, Lincoln then wrote a fifth draft, which was accepted for the purpose requested. The Bliss copy, named for Colonel Alexander Bliss, Bancroft's stepson and publisher of Autograph Leaves, is the only draft to which Lincoln affixed his signature. Lincoln is not known to have made any further copies of the Gettysburg Address. Because of the apparent care in its preparation, and in part, because Lincoln provided a title and signed and dated this copy, it has become the standard version of the address and the source for most facsimile reproductions of Lincoln's Gettysburg Address. It is the version that is inscribed on the South wall of the Lincoln Memorial.

This draft is now displayed in the Lincoln Room of the White House, a gift of Oscar B. Cintas, former Cuban Ambassador to the United States. Cintas, a wealthy collector of art and manuscripts, purchased the Bliss copy at a public auction in 1949 for $54,000 ($0 as of 2024), at that time the highest price ever paid for a document at public auction. Cintas' properties were claimed by the Castro government after the Cuban Revolution in 1959, but Cintas, who died in 1957, willed the Gettysburg Address to the American people, provided it would be kept at the White House, where it was transferred in 1959.

Garry Wills concluded the Bliss copy "is stylistically preferable to others in one significant way: Lincoln removed 'here' from 'that cause for which they (here) gave ...' The seventh 'here' is in all other versions of the speech." Wills noted the fact that Lincoln "was still making such improvements", suggesting Lincoln was more concerned with a perfected text than with an "original" one.

From November 21, 2008, to January 1, 2009, the Albert H. Small Documents Gallery at the Smithsonian Institution National Museum of American History hosted a limited public viewing of the Bliss copy, with the support of then-First Lady Laura Bush. The museum also launched an online exhibition and interactive gallery to enable visitors to look more closely at the document.

Associated Press report
Another contemporary source of the text is the Associated Press dispatch, transcribed from the shorthand notes taken by reporter Joseph L. Gilbert. It also differs from the drafted text in a number of minor ways.

Contemporary sources and reaction

Eyewitness reports vary as to their view of Lincoln's performance. In 1931, the printed recollections of 87-year-old Mrs. Sarah A. Cooke Myers, who was 19 when she attended the ceremony, suggest a dignified silence followed Lincoln's speech. "I was close to the President and heard all of the Address, but it seemed short. Then there was an impressive silence like our Menallen Friends Meeting. There was no applause when he stopped speaking." According to historian Shelby Foote, after Lincoln's presentation, the applause was delayed, scattered, and "barely polite". In contrast, Pennsylvania Governor Andrew Gregg Curtin maintained, "He pronounced that speech in a voice that all the multitude heard. The crowd was hushed into silence because the President stood before them ... It was so Impressive! It was the common remark of everybody. Such a speech, as they said it was!"

In an oft-repeated legend, Lincoln is said to have turned to his bodyguard Ward Hill Lamon and remarked that his speech, like a bad plow, "won't scour". According to Garry Wills, however, this statement largely originates from Lamon's unreliable recollections and is not accepted as fact. In Garry Wills's view, " had done what he wanted to do ".

In a letter to Lincoln written the following day, Everett praised the President for his eloquent and concise speech, saying, "I should be glad if I could flatter myself that I came as near to the central idea of the occasion, in two hours, as you did in two minutes." Lincoln replied that he was glad to know the speech was not a "total failure".

Other public reaction to the speech was divided along partisan lines. The Democratic-leaning Chicago Times observed, "The cheek of every American must tingle with shame as he reads the silly, flat and dishwatery utterances of the man who has to be pointed out to intelligent foreigners as the President of the United States." In contrast, the Republican-leaning The New York Times was complimentary and printed the speech. In Massachusetts, the Springfield Republican also printed the entire speech, calling it "a perfect gem" that was "deep in feeling, compact in thought and expression, and tasteful and elegant in every word and comma". The Republican predicted that Lincoln's brief remarks would "repay further study as the model speech".

In 2013, on the sesquicentennial of the address, The Patriot-News in Harrisburg, Pennsylvania, retracted its original reaction ("silly remarks" deserving "the veil of oblivion", writing: "Seven score and ten years ago, the forefathers of this media institution brought forth to its audience a judgment so flawed, so tainted by hubris, so lacking in the perspective history would bring, that it cannot remain unaddressed in our archives. ... the Patriot & Union failed to recognize [the speech's] momentous importance, timeless eloquence, and lasting significance. The Patriot-News regrets the error."

Foreign newspapers also criticized Lincoln's remarks. The Times of London reported, "The ceremony [at Gettysburg] was rendered ludicrous by some of the luckless sallies of that poor President Lincoln."

Congressman Joseph A. Goulden, then an eighteen-year-old school teacher, was present and heard the speech. He served in the United States Marine Corps during the war, and later had a successful career in insurance in Pennsylvania and New York City before entering Congress as a Democrat. In his later life, Goulden was often asked about the speech, since the passage of time made him one of a dwindling number of individuals who had been present for it. He commented on the event and Lincoln's speech in favorable terms, naming Lincoln's address as one of the inspirations for him to enter military service. Goulden's recollections included remarks to the House of Representatives in 1914.

Audio recollections
William R. Rathvon is the only known eyewitness of both Lincoln's arrival at Gettysburg and the address itself to have left an audio recording of his recollections. One year before his death in 1939, Rathvon's reminiscences were recorded on February 12, 1938, at the Boston studios of radio station WRUL, including his reading the address, itself, and a 78 RPM record was pressed. The title of the 78 record was "I Heard Lincoln That Day – William R. Rathvon, TR Productions". A copy wound up at National Public Radio (NPR) during a "Quest for Sound" project in 1999.

Like most people who came to Gettysburg, the Rathvon family was aware that Lincoln was going to make some remarks. The family went to the town square where the procession was to form to go out to the cemetery that had not been completed yet. At the head of the procession rode Lincoln on a gray horse preceded by a military band that was the first the young boy had ever seen. Rathvon describes Lincoln as so tall and with such long legs that they went almost to the ground; he also mentions the long eloquent speech given by Edward Everett of Massachusetts whom Rathvon accurately described as the "most finished orator of the day". Rathvon then goes on to describe how Lincoln stepped forward and "with a manner serious almost to sadness, gave his brief address". During the delivery, along with some other boys, young Rathvon wiggled his way forward through the crowd until he stood within 15 ft of Lincoln and looked up into what he described as his "serious face". Rathvon recalls candidly that, although he listened "intently to every word the president uttered and heard it clearly", he explains, "boylike, I could not recall any of it afterwards". But he explains that if anyone said anything disparaging about "honest Abe", there would have been a "junior battle of Gettysburg". In the recording Rathvon speaks of Lincoln's speech allegorically "echoing through the hills".

Photographs
The only known and confirmed photograph of Lincoln at Gettysburg, taken by photographer David Bachrach, was identified in the Mathew Brady collection of photographic plates in the National Archives and Records Administration in 1952. The identification was made by Josephine Cobb, an archivist who enlarged a mislabeled glass plate negative to reveal the president's presence among the crowd. While Lincoln's speech was short and may have precluded multiple pictures of him while speaking, he and the other dignitaries sat for hours during the rest of the program. A popular explanation for the Bachrach photo suggests that Lincoln's brief address, which followed a lengthy speech by Everett, caught photographers by surprise. As a result, they supposedly could only take a photo of Lincoln after the speech had ended. This theory has been questioned, however, with evidence suggesting that the photo was possibly taken before the Gettysburg Address and without any intention to capture the President from such a long distance.

Usage of "under God"
The words "under God" do not appear in the Nicolay and Hay drafts but are included in the three later copies (Everett, Bancroft, and Bliss). Accordingly, some skeptics maintain that Lincoln did not utter the words "under God" at Gettysburg. However, at least three reporters telegraphed the text of Lincoln's speech on the day the Address was given with the words "under God" included. Historian William E. Barton argues that:

"Every stenographic report, good, bad and indifferent, says 'that the nation shall, under God, have a new birth of freedom.' There was no common source from which all the reporters could have obtained those words but from Lincoln's own lips at the time of delivery. It will not do to say that [Secretary of War] Stanton suggested those words after Lincoln's return to Washington, for the words were telegraphed by at least three reporters on the afternoon of the delivery."

The reporters present included Joseph Gilbert, from the Associated Press; Charles Hale, from the Boston Advertiser; John R. Young (who later became the Librarian of Congress), from the Philadelphia Press; and reporters from the Cincinnati Commercial, New York Tribune, and The New York Times. Charles Hale "had notebook and pencil in hand, [and] took down the slow-spoken words of the President". "He took down what he declared was the exact language of Lincoln's address, and his declaration was as good as the oath of a court stenographer. His associates confirmed his testimony, which was received, as it deserved to be, at its face value." One explanation is that Lincoln deviated from his prepared text and inserted the phrase when he spoke. Ronald C. White, visiting professor of history at the University of California, Los Angeles and professor of American religious history emeritus at the San Francisco Theological Seminary, wrote in this context of Lincoln's insertion and usage of "under God":

"It was an uncharacteristically spontaneous revision for a speaker who did not trust extemporaneous speech. Lincoln had added impromptu words in several earlier speeches, but always offered a subsequent apology for the change. In this instance, he did not. And Lincoln included 'under God' in all three copies of the address he prepared at later dates. 'Under God' pointed backward and forward: back to 'this nation', which drew its breath from both political and religious sources, but also forward to a 'new birth'. Lincoln had come to see the Civil War as a ritual of purification. The old Union had to die. The old man had to die. Death became a transition to a new Union and a new humanity."

The phrase "under God" was used frequently in works published before 1860, usually with the meaning "with God's help".

Platform location
Outside of either entrance to the National Cemetery, twin historical markers read:

"Nearby, Nov. 19, 1863, in dedicating the National Cemetery, Abraham Lincoln gave the address which he had written in Washington and revised after his arrival at Gettysburg the evening of November 18."

Directly inside the Taneytown Road entrance are the Lincoln Address Memorial and Rostrum, which has hosted speeches by five U.S. Presidents. Lincoln was not one of them, and a small metal sign near the speech memorial stirs controversy by stating:

"The Address was delivered about 300 yards from this spot along the upper Cemetery drive. The site is now marked by the Soldiers' National Monument."

Holding title as the Traditional Site, the validity of the Soldiers' National Monument has been challenged by platform occupants (in the distant past) and by (relatively recent) photographic analyses. Based upon a pair of photographic analyses, the Gettysburg National Military Park (G.N.M.P.) has placed a marker (near 39°49.199′N 77°13.840′W) which states, "The location [of the platform] was never marked, but is believed to be in Evergreen Cemetery, on the other side of the iron fence."

The observer of this newer marker stands facing the fence which separates the two adjacent cemeteries (one public and one private). Another heavy endorsement of the Traditional Site, this one in bronze and placed by Lincoln's native Commonwealth, stands nearby.

Absent an original and enduring marker, the location of the platform is in the hands of rhetoricians and scholars. The Superintendent of Evergreen Cemetery, Brian Kennell, emphatically endorses the findings of William Frassanito's photographic analysis.

Pre-modern
Colonel W. Yates Selleck was a marshal in the parade on Consecration Day and was seated on the platform when Lincoln made the address. Selleck marked a map with the position of the platform and described it as "350 ft almost due north of Soldiers' National Monument, 40 ft from a point in the outer circle of lots where [the] Michigan and New York [burial sections] are separated by a path". A location which approximates this description is 39°49.243′N, 77°13.869′W.

As pointed out in 1973 by retired park historian Frederick Tilberg, the Selleck Site is 25 ft lower than the crest of Cemetery Hill, and only the crest presents a panoramic view of the battlefield. A spectacular view from the location of the speech was noted by many eyewitnesses, is consistent with the Traditional Site at the Soldiers' National Monument (and other sites on the crest) but is inconsistent with the Selleck Site.

The Kentucky Memorial, erected in 1975, is directly adjacent to the Soldiers' National Monument, and states, "Kentucky honors her son, Abraham Lincoln, who delivered his immortal address at the site now marked by the soldiers' monument." With its position at the center of the concentric rings of soldiers' graves and the continuing endorsement of Lincoln's native state the Soldiers' National Monument persists as a credible location for the speech.

Writing a physical description of the layout for the Gettysburg National Cemetery under construction in November 1863, the correspondent from the Cincinnati Daily Commercial described the dividing lines between the state grave plots as "the radii of a common center, where a flag pole is now raised, but where it is proposed to erect a national monument". With the inclusion of this quotation Tilberg inadvertently verifies a central principle of future photographic analyses—a flagpole, rather than the speakers' platform, occupied the central point of the soldiers' graves. In fact, the precision of the photo-analyses relies upon the coincidence of position between this temporary flag pole and the future monument.

Confusing to today's tourist, the Kentucky Memorial is contradicted by a newer marker which was erected nearby by the Gettysburg National Military Park and locates the speakers' platform inside Evergreen Cemetery. Similarly, outdated National Park Service documents which pinpoint the location at the Soldiers' National Monument have not been systematically revised since the placement of the newer marker. Miscellaneous web pages perpetuate the Traditional Site.

2D and optical stereoscopy
In 1982, Senior Park Historian Kathleen Georg Harrison first analyzed photographs and proposed a location in Evergreen Cemetery but has not published her analysis. Speaking for Harrison without revealing details, two sources characterize her proposed location as "on or near [the] Brown family vault" in Evergreen Cemetery.

William A. Frassanito, a former military intelligence analyst, documented a comprehensive photographic analysis in 1995, and it associates the location of the platform with the position of specific modern headstones in Evergreen Cemetery. According to Frassanito, the extant graves of Israel Yount (died 1892)(39.81967°N, -77.23075°W), John Koch (died 1913)(39.81973°N, -77.23078°W), and George E. Kitzmiller (died 1874)(39.8197°N, -77.23068°W) are among those which occupy the location of the 1863 speaker's stand.

3D photo-rendering and -animation
Over the course of many years, an Assistant Professor of New Media at the University of North Carolina at Asheville, Christopher Oakley, and his students have labored to produce and relentlessly perfect "a lifelike virtual 3-D re-creation of Lincoln delivering the Gettysburg Address" as part of the Virtual Lincoln Project. One result was revealed when “Placing the Platform: Using 3D Technology to Pinpoint Lincoln at Gettysburg” was presented on November 18, 2022, at the Lincoln Forum XXVII in Gettysburg.

As a starting point, the project modeled the topography around Cemetery Hill, the Gatehouse at Evergreen Cemetery and the documented positions of nonextant objects which appear in photographs (the poplar tree, the flag pole and the Duttera House among them) using 3-D animation software Maya. Next, the platform and its occupants were modeled. Finally, the approximate positions of the cameras were placed into the 3-D environment, and the overall model was iteratively refined. By reproducing the appearance of the four known photographs, taken distantly from one another in 1863, Lincoln and the platform have been placed in virtual reality.

Oakley's model shows the platform straddling the iron fence between the Soldiers' National Cemetery and Evergreen Cemetery. It increases the size of the platform and changes its shape from rectangular, as previous researchers have maintained, to trapezoidal. Most significantly, the speaker's position occupies a portion of the platform over the grounds of the Soldiers' National Cemetery.

William Frassanito's analysis is based upon two of the four photographic perspectives which were employed by Oakley to validate his 3D model. Frassanito assesses one of his sources by stating, "This view [by Weaver] was probably not taken from the second-story window of the gatehouse itself." Via enlargement of a Gardner photograph (taken from the opposite direction), John J. Richter may have identified a photographer with a camera in this exact window, thereby weakening the contribution of the Weaver photograph to Frassanito's conclusions. Oakley's proprietary 3D model utilizes the position of Weaver's camera as suggested by Richter.

Resolution
The GNMP marker, Wills's interpretation of Harrison's analysis, the Frassanito analysis, and the Oakley analysis concur that the platform was located entirely or mostly in private Evergreen Cemetery, rather than public Soldiers' National Cemetery. The National Park Service's National Cemetery Walking Tour brochure is one NPS document which agrees: "The Soldiers' National Monument, long misidentified as the spot from which Lincoln spoke, honors the fallen soldiers. [The location of the speech] was actually on the crown of this hill, a short distance on the other side of the iron fence and inside the Evergreen Cemetery, where President Lincoln delivered the Gettysburg Address to a crowd of some 15,000 people."

The locations determined by the Harrison/Wills, Frassanito, and Oakley analyses differ by approximately 40 yards. Frassanito has documented 1) his own conclusion, 2) his own methods and 3) a refutation of the Harrison site, but neither the GNMP nor Harrison has provided any documentation. Oakley's interpretation was only made public in 2022 and is still under review. Each of the four points to a location in Evergreen Cemetery, as do modern NPS publications.

Although Lincoln dedicated the Gettysburg National Cemetery, the monument at the Cemetery's center actually has nothing to do with Lincoln or his famous speech. Intended to symbolize Columbia paying tribute to her fallen sons, its appreciation has been commandeered by the thirst for a tidy home for the speech. Freeing the Cemetery and Monument to serve their original purpose, honoring of Union departed, is as unlikely as a resolution to the location controversy and the erection of a public monument to the speech in the exclusively private Evergreen Cemetery.

Legacy
The importance of the Gettysburg Address in the history of the United States is underscored by its enduring presence in American culture. In addition to its prominent place carved into a stone cella on the south wall of the Lincoln Memorial in Washington, D.C., the Gettysburg Address is frequently referred to in works of popular culture, with the implicit expectation that contemporary audiences will be familiar with Lincoln's words.

In the many generations that have passed since the Address, it has remained among the most famous speeches in American history and is often taught in classes about history or civics. Lincoln's Gettysburg Address is itself referenced in another of those famed orations, Martin Luther King Jr.'s "I Have a Dream" speech. Standing on the steps of the Lincoln Memorial in August 1963, King began with a reference, by the style of his opening phrase, to President Lincoln and his enduring words: "Five score years ago, a great American, in whose symbolic shadow we stand today, signed the Emancipation Proclamation. This momentous decree came as a great beacon light of hope to millions of Negro slaves who had been seared in the flames of withering injustice."

Phrases from the Address are often used or referenced in other works. The current Constitution of France states that the principle of the French Republic is "gouvernement du peuple, par le peuple et pour le peuple ("government of the people, by the people, and for the people"), a literal translation of Lincoln's words. Sun Yat-Sen's "Three Principles of the People" as well as the preamble for the 1947 Constitution of Japan were also inspired from that phrase. The aircraft carrier USS Abraham Lincoln (CVN-72) has as its ship's motto the phrase "shall not perish".

U.S. Senator Charles Sumner of Massachusetts wrote of the address and its enduring presence in American culture after Lincoln's assassination in April 1865: "That speech, uttered at the field of Gettysburg ... and now sanctified by the martyrdom of its author, is a monumental act. In the modesty of his nature he said 'the world will little note, nor long remember what we say here; but it can never forget what they did here.' He was mistaken. The world at once noted what he said, and will never cease to remember it."

In January 1961 John F. Kennedy tasked his speech writer Ted Sorensen to study the Gettysburg Address in order to help him with his own inaugural address. Sorensen drew many lessons from the Gettysburg Address which according to Sorensen included rhetoric devices used by many speech writers like alliterations, rhymes, repetitions as well as contrast and balance.

U.S. President John F. Kennedy stated in July 1963 about the battle and Lincoln's speech: "Five score years ago the ground on which we here stand shuddered under the clash of arms and was consecrated for all time by the blood of American manhood. Abraham Lincoln, in dedicating this great battlefield, has expressed, in words too eloquent for paraphrase or summary, why this sacrifice was necessary."

In 2015, the Abraham Lincoln Presidential Library Foundation compiled Gettysburg Replies: The World Responds to Abraham Lincoln's Gettysburg Address. The work challenges leaders to craft 272 word responses to celebrate Lincoln, the Gettysburg Address, or a related topic. One of the replies was by astrophysicist Neil deGrasse Tyson in which he made the point that one of Lincoln's greatest legacies was establishing, in the same year of the Gettysburg Address, the National Academy of Sciences, which had the longterm effect of "setting our Nation on a course of scientifically enlightened governance, without which we all may perish from this Earth".

Envelope and other myths
A common American myth about the Gettysburg Address is that Lincoln quickly wrote the speech on the back of an envelope while on the train. This widely held misunderstanding may have originated with a popular book, The Perfect Tribute, by Mary Raymond Shipman Andrews (1906), which was assigned reading for generations of schoolchildren, sold 600,000 copies when published as a standalone volume, and was twice adapted for film.

Other lesser-known claims include Harriet Beecher Stowe's assertion that Lincoln had composed the address "in only a few moments", and that of industrialist Andrew Carnegie, who claimed to have personally supplied Lincoln with a pen.

Popular culture
A Lincoln Portrait is a classical orchestral work written by the American composer Aaron Copland in which the closing phrases of the Gettysburg address are intoned at the conclusion of the narrated Lincoln quotations which lead to the orchestral closing crescendo. The work involves a full orchestra, with particular emphasis on the brass section at climactic moments. The work is narrated with the reading of excerpts of Abraham Lincoln's great documents, including the Gettysburg Address. The intoned reading from the Address uses only the last two sentences starting with the words, "That from these honored dead ...".

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title: Gettysburg Address