Morpeth, Northumberland

# Morpeth, Northumberland

Morpeth is a historic market town in Northumberland, North East England, lying on the River Wansbeck. Nearby towns include Ashington and Bedlington. In the 2011 census, the population of Morpeth was given as 14,017, up from 13,833 in the 2001 census. The earliest evidence of settlement is believed to be from the Neolithic period, and some Roman artifacts have also been found. The first written mention of the town is from 1080, when the de Merlay family was granted the barony of Morpeth. The meaning of the town's name is uncertain, but it may refer to its position on the road to Scotland and a murder which occurred on that road. The de Merlay family built two castles in the town in the late 11th century and the 13th century. The town was granted its coat of arms in 1552. By the mid-1700s it had become one of the main markets in England, having been granted a market charter in 1200, but the opening of the railways in the 1800s led the market to decline. The town's history is celebrated in the annual Northumbrian Gathering.

Morpeth is governed by Northumberland County Council and Morpeth Town Council. The town is split into three wards – North, Kirkhill and Stobhill – for the purposes of parish elections. In 2008 the town suffered a severe flood, which was repeated in 2012, resulting in the construction of new flood defences. Morpeth railway station is on the east coast line and a curve to the south of it has caused several rail crashes. Several sports teams compete in Morpeth, with Morpeth Town A.F.C. having been the winner of the FA Vase in 2016. The town hosted its own Olympics from 1873 to 1958. Two middle schools, a high school and seven first schools are situated in Morpeth, as well as several churches of Anglican, Roman Catholic, United Reformed and Methodist denominations. Morpeth's Carlisle Park, the recipient of several awards, contains one of the four floral clocks in England.

## History

Morpeth was founded at a crossing point of the River Wansbeck. Remains from prehistory are scarce, but the earliest evidence of occupation found is a stone axe thought to be from the Neolithic period. There is a lack of evidence of activity during the Roman occupation of Britain, although there were probably settlements in the area at that time. The first written reference is from 1080 when William de Merlay was rewarded for his part in suppressing a rebellion in Northumbria with "the Barony of Morthpeth stretching from the Tyne to the Coquet". The name derives from Old English morð pæð and literally means "murder path"; writing in 1666, the antiquarian John Stainsby attributed this moniker to "the many robberies and murders in those parts committed".

The barony of Morpeth was granted to the de Merlay family in around 1080, and by 1095 a motte-and-bailey castle had been built by William de Merlay. It is uncertain whether there was any settlement at Morpeth at the time that the barony was created, and documents relating to the foundation of an abbey in 1137 refer to the "new town of Morpeth". Newminster Abbey, located on the outskirts of Morpeth, was founded in 1138 by William's son, Ranulf de Merlay, lord of Morpeth, and his wife, Juliana, daughter of Gospatric II, Earl of Lothian, as one of the first daughter houses of Fountains Abbey. King John granted a market charter for the town to Roger de Merlay in 1200. It became one of the main markets in Northern England by the mid-1700s and by the mid 18th century was one of the key cattle markets in England selling cattle driven by drovers over the border from Scotland; however, the opening of the railways made transport to Newcastle easier in the 19th century, and the market accordingly declined. The market is still held on Wednesdays.

The town was badly damaged by fire set by the barons in 1215 during the First Barons' War, in an attempt to block the military operations of King John. Whilst it is common report that the motte-and-bailey castle was burnt down by King John in 1216 and a new Morpeth Castle was built later in the 13th century by Ranulph de Merlay, to the south of Haw Hill, there is no firm evidence that King John destroyed the castle and an alternative narrative suggests that the second castle was in fact "completed by William de Merlay (the 2nd) in the year of his death" (c. 1170). In the 13th century, a stone bridge was built over the Wansbeck in Morpeth, to the west of the current bridge, replacing the ford previously in use in Morpeth. For some months in 1515–16, Margaret Tudor (Henry VIII's sister) who was the Queen Consort of Scotland (James IV's widow), had laid ill in Morpeth Castle, having been brought there from Harbottle Castle. The only remains of the castle are the inner gatehouse, which was restored by the Landmark Trust, and parts of the ruined castle walls.

In 1540, Morpeth was described by the royal antiquary John Leland as "long and metely well-builded, with low houses" and "a far fairer town than Alnwick". During the 1543–51 war of the Rough Wooing, Morpeth was occupied by a garrison of Italian mercenaries, who "pestered such a little street standing in the highway" by killing deer and withholding payment for food. In 1552, William Hervey, Norroy King of Arms, granted the borough of Morpeth a coat of arms. The arms were the same as those granted to Roger de Merlay, but with the addition of a gold tower. In the letters patent, Hervey noted that he had included the arms of the "noble and valyaunt knyght ... for a p'petuall memory of his good will and benevolence towardes the said towne".

Morpeth was a borough by prescription, but received its first charter of confirmation from Charles II. The corporation it created was controlled by seven companies: the Merchant Tailors, the Tanners, the Fullers and Dyers, the Smiths, the Cordwainers, the Weavers and the Butchers. This remained the governing charter until the borough was reformed by the Municipal Corporations Act 1835. During the Second World War, RAF Morpeth, an air-gunnery training school, opened at nearby Tranwell.

The town and the county's history and culture are celebrated at the annual Northumbrian Gathering. The gathering is held over a weekend in mid-April and includes the Border Cavalcade and Pageant. The 50th gathering took place in 2017.

## Governance

Morpeth has two tiers of local government.

The lower tier is Morpeth Town Council, which has 15 members. Morpeth is a civil parish with the status of a town. For the purposes of parish elections the town is divided into three wards: North, Kirkhill and Stobhill, each returning five town councillors. Each ward also elects one County Councillor. In May 2021, the political make up of the Town Council was ten Conservatives, two Liberal Democrats, two Green and one Labour member.

The upper tier of local government is Northumberland County Council, which meets at County Hall in Morpeth. Since April 2009 the county council has been a unitary authority. Previous to this there was an intermediate tier, the non-metropolitan district of Castle Morpeth, which has been abolished along with all other districts in the county. The county council has 67 councillors, of whom three represent Morpeth, one each from the electoral wards of Morpeth Kirkhill, Morpeth North and Morpeth Stobhill. The 2017 and 2021 County Council elections both elected three Conservative councillors for the three wards.

## Climate

Cockle Park, located slightly north of Morpeth, contains a Met Office weather station, founded in 1897.

### 2008 and 2012 floods

On 6 September 2008, Morpeth suffered a severe flood, causing damage to 1,000 properties and leading 400 residents to be evacuated. The town's flood defences were breached after 12 hours, when a month's worth of rain fell on Morpeth.

In September 2012, flooding occurred again, causing damage to properties, although floodwaters were reportedly 3 feet (1 m) shallower than in 2008.

### Flood defences

Work on flood defences started in 2013 in response to the 2008 floods. New flood defences were built in the town centre and a dam with a storage reservoir was built on the Mitford Estate. A second £27m dam was completed in May 2017 to reduce flooding from the Cotting Burn and marked the completion of the Morpeth flood defence plan.

## Transport

### Road

The A1, the longest numbered road in the UK, used to pass through Morpeth until the bypass was opened in 1970. Other roads that pass though the town are: A192, A196, A197, B1337, B6343 and the B6524.

Morpeth Northern Bypass

The Morpeth Northern Bypass was a project to decrease traffic congestion in Morpeth town centre and decrease journey times from Pegswood, Ashington and Newbiggin to the A1 and beyond. The Bypass follows on from the Pegswood Bypass at Whorral Bank Roundabout and continues to the St George's Roundabout and then onto Northgate Roundabout and St Leonard's A1 Junction. The Project was completed in 2017, which has allowed increased connectivity to SE Northumberland and beyond.

### Rail

Morpeth's railway station is on the main East Coast Main Line which runs between London and Edinburgh. To the south of the station is a sharp curve which has been the scene of several train crashes. A non-passenger line operates between Morpeth and Bedlington. A former line, closed in 1966, ran west from Morpeth to Scots Gap (from where there was a branch line to Rothbury), then west to Redesmouth, and lastly south to Hexham.

### Bus

Arriva North East are the main operator of bus services in the town, with services going to nearby towns and villages such as Pegswood, Guide Post, Ashington, Bedlington or to Newcastle, Alnwick, Amble, Berwick or Widdrington.

## Education

The local state school, King Edward VI School, was originally founded as a chantry school in the early 14th century and was located in the Morpeth Chantry. The school was refounded in 1552 by royal charter as the Free Grammar School of King Edward the Sixth, being commonly referred to as the Morpeth Grammar School by locals. The school was renamed to King Edward VI Grammar School by 1947 and in the 1970s lost its grammar school status, becoming a comprehensive under the current name.

The town has two middle schools, Newminster and Chantry, which are built next door to one another. It also has several first schools: Abbeyfields First School in Kirkhill, Morpeth First School in Loansdean to the south of the town, Stobhillgate First School in the Stobhillgate housing estate, and Morpeth All Saints' Church of England-aided First School in Lancaster Park, which is located north of the town. Additionally, St. Robert's R.C. First School, a primary school for Roman Catholics, is located in Oldgate, Morpeth.

## Religious sites

### Church of England

The ancient Church of England parish church of Morpeth is St Mary's at High Church, which was the main Anglican place of worship in the area until the 1840s. The church is mostly in the 14th century style. The grave of Emily Wilding Davison lies in St Mary's graveyard.

In 1843, a public meeting was called to address the lack of attendance at the church, and it was found that the walk to the current church, then on the southern edge of the town, was too much for many of the parishioners. From this meeting, it was decided to build a new church in the town centre and accordingly, the church of St James the Great was consecrated for worship on 15 October 1846. Benjamin Ferrey designed the church in a "Neo-Norman" style, based on the 12th century Monreale Cathedral, Sicily.

A third parish church, St Aidan's, was founded as a mission church in 1957, located on the Stobhill estate on the south-east of the town.

### Roman Catholic Church

Morpeth's Roman Catholic Church, St Robert of Newminster Church, was built off Oldgate on land adjacent to Admiral Lord Collingwood's house. It was consecrated on 1 August 1850 by the Right Reverend William Hogarth, Bishop of Samosata (later Bishop of Hexham). Collingwood House is now the presbytery (residence) for the priest in charge of the Church.

### United Reformed Church

Morpeth has had a Presbyterian ministry since 1693. Their first service was held in a tannery loft in the town in February 1693 and in 1721 a chapel was built in Cottingwood Lane, which still exists as a private home. The construction of St. George's United Reformed Church began in 1858 and the first service in the new building was held on 12 April 1860. The Church stands immediately to the north of the Telford Bridge and is in the style of the early English era, containing a stained glass rose window and an octagonal spirelet.

### Methodist Church

The present Methodist Church in Howard Terrace was opened as a Primitive Methodist place of worship on 24 April 1905. Designed by J. Walton Taylor, it was built from local quarry stone. Although the Primitive Methodists were united with the Wesleyan Church to form the Methodist Church of Great Britain in 1932, a separate Wesleyan Church continued to function in Manchester Street until 1964, when the congregations were united at Howard Terrace. The former Wesleyan Church (built in 1883) is currently used as the Boys' Brigade headquarters.

## Sport

Morpeth Town A.F.C., Morpeth RFC and the Morpeth Golf Club play competitively within Morpeth. In addition, the Morpeth Harriers compete in athletics. The town also offers opportunities to play sport on a non-competitive basis through facilities such as Carlisle Park, the common for playing golf and football, and the Riverside leisure centre for swimming, indoor sports and fitness gym activities. Morpeth Town A.F.C. was the 2016 winner of the FA Vase.

The Morpeth Olympic Games, a professional event consisting mainly of athletics and wrestling, were staged from 1873 until 1958, barring interruptions during the two world wars. The Games were held on the Old Brewery Field until 1896, then at Grange House Field until the First World War. After two years at the town's cricket pitch at Stobhill (1919–20), the Olympics moved to Mount Haggs Field until 1939, and then back to Grange House Field after the war until the end of the games in 1958.

In 1730, a racecourse was built for horse racing, which was used until 1854, when the racetrack was replaced with St. George's Hospital.

The town was the start point of the Morpeth To Newcastle Road Race. It was held annually on New Year's Day from 1902 to 2004, when insurance and policing costs became prohibitively high, and winners included Commonwealth champion Jack Holden and Olympic medallist Mike McLeod.

## Landmarks

The historical layout of central Morpeth consisted of Bridge Street, Oldgate Street and Newgate Street, with burgage plots leading off them. Traces of this layout remain: Old Bakehouse Yard off Newgate Street is a former burgage plot, as is Pretoria Avenue, off Oldgate. The town stands directly on what used to be the Great North Road, the old coaching route between London and Edinburgh.

Carlisle Park is located on the southern bank of the River Wansbeck in Morpeth. The park has the William Turner Garden, one of the only four floral clocks in England, a statue of Emily Wilding Davison, as well as other facilities and attractions. Morpeth's Mafeking Park, at the bottom of Station Bank, was unsuccessfully put forward by locals to be listed as the smallest park in the world in the Guinness Book of Records.

Other landmarks are:

- Morpeth Clock Tower, a free-standing 17th century clock tower
- Morpeth Town Hall, originally designed by Sir John Vanbrugh (rebuilt 1869)
- Collingwood House, the Georgian home of Admiral Lord Collingwood
- Morpeth Chantry, a 13th-century chapel that now houses the town's tourist information centre and the Morpeth Chantry Bagpipe Museum
- Morpeth Castle, which stands on a hill to the south, is now operated by the Landmark Trust as holiday accommodation
- A nuclear bunker located underneath Morpeth County Hall
- A gateway on High Stanners framed by a whale's jawbone
- Ruins of Newminster Abbey, a former Cistercian abbey about one mile to the west of Morpeth
- Morpeth Court, former courthouse and prison, now converted into apartments

## Notable people

- Bill Rutherford (1955-), Professor and Chair in Biochemistry of Solar energy in the Department of Life sciences at Imperial College London.
- Lawrence William Adamson (1829–1911), High Sheriff of Northumberland, who died at Linden Hall near Morpeth in 1911
- James (Jim) Alder (born 1940), athlete, who spent his childhood in Morpeth after being adopted by Adler family

- Emerson Muschamp Bainbridge (1817–1892), founder of Bainbridge Department Store – the first such store in the world – in Newcastle upon Tyne, who, from 1877, lived near Morpeth at Eshott Hall
- Arthur Bigge, 1st Baron Stamfordham (1849–1931), born at Linden Hall, near Morpeth, who became private secretary to Queen Victoria and George V
- Robert Blakey (1795–1878), radical journalist and philosopher, born in Manchester Street, Morpeth

- Luke Clennell (1781–1840), engraver and painter, born in Morpeth
- Vice Admiral Cuthbert Collingwood (1748–1810), Royal Navy Admiral. He lived at Collingwood House in Oldgate and once said "Whenever I think how I am to be happy again, my thoughts carry me back to Morpeth".

- Emily Wilding Davison, a suffragette who was killed when she fell under the King's horse during the Epsom Derby in 1913. Following her funeral in London, her coffin was brought by train to Morpeth for burial in St Mary's churchyard.

- William Elliott, Baron Elliott of Morpeth (1920–2011), Conservative politician born in Morpeth

- Toby Flood (born 1985), rugby union player for Leicester Tigers and England, who attended Morpeth Chantry School

- Hamish Turnbull (born 1999), Cyclist representing British Cycling and Great Britain.

- John Cuthbert Hedley (1837–1913), Benedictine monk and Roman Catholic Bishop of Newport born at Carlisle House, Morpeth
- Charles Howard, 3rd Earl of Carlisle (1669–1738), MP for Morpeth in 1689–1692

- Robert Morrison (1782–1834), translator of the Bible into Chinese and first Protestant missionary in China, born in Buller's Green, Morpeth

- John Peacock (c. 1756–1817), piper, born in Morpeth

- John Urpeth Rastrick (1780–1856), railway engineer, born in Morpeth
- Joe Robinson (1919–1991), footballer, born in Morpeth, who played for Blackpool in the 1948 FA Cup Final

- Walter Trevelyan (1821 – 1894), first-class cricketer and barrister, born in Morpeth
- William Turner (naturalist) (c. 1508 – 13 July 1568), an English divine and reformer, physician and natural historian. The William Turner Garden is situated in Carlisle Park, Morpeth.

- Dr. N. T. Wright (born 1948), Anglican theologian and author, born in Morpeth

## See also

- Viscount Morpeth, the heir apparent to the Earl of Carlisle.

Town in Northumberland, England


Constitution Center (Washington, D.C.)

# Constitution Center (Washington, D.C.)

Constitution Center (formerly known as the David Nassif Building) is an office building located at 400 7th Street SW in Washington, D.C. It is 140 feet (43 m) high and has 10 floors. Covering an entire city block, it is the largest privately owned office building in the District of Columbia. Current tenants include the Federal Housing Finance Agency and the Office of the Comptroller of the Currency. As of February 2014, Constitution Center was worth \$725.8 million, making it the most valuable taxable property in the city.

## Original structure

In the 1950s, the U.S. Congress, then the governing institution of the District of Columbia, undertook the Southwest D.C. urban renewal project, the first in the capital district and one of the earliest such programs in the nation. In 1946, Congress passed the District of Columbia Redevelopment Act, which established the District of Columbia Redevelopment Land Agency (RLA) and provided legal authority to clear land and funds to spur redevelopment in the capital. Congress also gave the National Capital Planning Commission (NCPC) the authority to designate which land would be redeveloped, and how. The RLA was not funded, however, until passage of the Housing Act of 1949. A 1950 study by the NCPC found that the small Southwest quarter of the city suffered from high concentrations of old and poorly maintained buildings, overcrowding, and threats to public health (such as lack of running indoor water, sewage systems, electricity, central heating, and indoor toilets). Competing visions for the redevelopment ranged from renovation to wholesale leveling of neighborhoods, but the latter view prevailed as more likely to qualify for federal funding. Original plans called for the demolition of almost all structures in Southwest Washington beginning in 1950, but legal challenges led to piecemeal razing of the area until the mid-1950s.

Issues surrounding the planning and construction of L'Enfant Plaza (immediately to the west of the site) delayed construction of any buildings on the block until the late 1960s. In 1963, the RLA purchased the land from the Westminster Memorial Church, Fifth Baptist Church, and homeowners. The United States Department of Health, Education and Welfare wished to purchase the site for its new headquarters, but the RLA declined to sell the property. (The federal government does not pay taxes on land and structures it owns, and the RLA wanted a private owner who would add to the tax base.) The RLA attempted to sell the land on January 29, 1965, but there were no buyers.

The building was constructed pursuant to an agreement between the General Services Administration (GSA) and Boston developer David Nassif, Sr. In July 1965, President Lyndon B. Johnson began planning to unite various disparate transportation agencies into a new United States Department of Transportation. GSA (the property owner and manager for the U.S. federal government) began seeking to lease or build a structure to house the new agency in late 1965. Donald T. Kirwan, chief of GSA's leasing division, knew Nassif from a previous lease negotiation, and discussed with him the siting of a building and its size. Nassif approached the RLA on April 21, 1966, and asked to buy the newly razed block of land bounded by 6th, 7th, D, and E Streets SW. In May 1967, GSA sent a letter to Nassif advising him that it was likely to lease the entire structure he intended to build. The \$5.9 million land purchase was finalized on October 30, 1967. The cost of the structure is unclear. On November 15, 1967, Nassif had secured a \$39 million construction loan. But The Washington Post pegged the cost of the building at \$27 million in July 1968. The newspaper said in August 1970 that the cost of the structure was \$26.5 million. The building was designed by architect Edward Durrell Stone, who also designed the John F. Kennedy Center for the Performing Arts. On April 11, 1968, GSA leased the entire building from Nassif for 20 years for \$98 million. John A. Volpe Construction was the chief contractor.

Construction began in July 1968 (although it was delayed for a very short time when unionized ironworkers at the site went on strike) and was completed in 1969. The main entrance faced 7th Street SW. It included a central courtyard (open to the sky) which featured a fountain, footpaths, benches, and landscaping. Four 15-foot (4.6 m) high arcades pierced the building in the center of the block on each side, creating access to the courtyard. The facade's vertical marble ribs were obtained from the same quarry near Carrara, Italy, that provided the marble for the Kennedy Center. The finished building had 10 floors, three basement floors, overhanging eaves, and 2,500,000 square feet (230,000 m2) of space (1,019,000 square feet (94,700 m2) of usable space). It was the largest privately owned office building in the city at the time.

Kirwan's contacts with Nassif later became the subject of a legal investigation. Kirwan not only shared inside information with Nassif about leasing plans of the GSA, he later invested in Nassif's D.C. business and became an officer in it. This relationship (Kirwan left GSA in December 1966, before the letter indicating intention to lease was set to Nassif), and GSA's irregular leasing of the building, became public knowledge in August 1970. An internal GSA audit was critical of the leasing process and the costs of the lease.

That same month, refinancing of the building was called into question. In the U.S., it is common business practice for the initial lender to provide an interim loan (the "construction loan") to build a building. The interim loan is then paid off by a second lender, who becomes the mortgage lender and receives payments from the building's owner. Riggs Bank, a local D.C. bank, had provided the interim construction loan to Nassif. The New York City Employees Retirement System was to have paid off this construction loan. That payment was halted when the loan officer Nassif had dealt with was indicted for taking bribes to approve loans. When the pension fund refused to provide the loan, Riggs Bank sued for payment and threatened to foreclose on the Nassif Building.

From 1969 until 2007, the Nassif Building served as the headquarters of the U.S. Department of Transportation (DOT). The building was designed to have removable interior walls to permit easy reconfiguration of the interior space. In November 1970, the federal government exercised its powers of eminent domain and seized control of the three-story basement parking garage from Nasif in order to provide inexpensive parking for DOT workers. Over the years, so many government workers complained of ailments while working in the structure that some believed it suffered from sick building syndrome. David Nassif Associates, owner of the building, disputed these claims. However, when the Department of Transportation announced it would leave the building in 2000, the owners promised a \$100 million renovation that included a new air ventilation and cleaning system as an inducement for the agency to stay. The owners also unsuccessfully sued the General Services Administration in 1999 to force it to renew the federal lease on the building. The Department of Transportation completed their move out of the Nassif Building and into their new headquarters in June 2007.

The L'Enfant Plaza Metro station opened an escalator entrance in the structure's north arcade on July 1, 1977. The entrance was one of two which opened that day (Metro Blue Line's opening day). The third entrance (inside the L'Enfant Promenade underground shopping center at L'Enfant Plaza) opened in October 1977. In June 1992, Virginia Railway Express opened the \$1.1 million VRE L'Enfant Station on Virginia Avenue SE (about a half block north of Constitution Center).

## Renovation

In 2006, Nassif Associates announced a \$220 million renovation of the building and renamed it "Constitution Center". SmithGroup was the architectural firm overseeing the redesign, and Davis Construction oversaw the construction.

The renovation included some of the highest security features of any building in the D.C. area. They included a central and perimeter security system; closing of the central plaza of the building, which, along with other changes, increased its interior footage by 80,000 square feet (7,400 m2); steel-jacketed underground parking garage columns capable of withstanding a powerful explosion; six fully staffed security screening points; concrete blockades built into the façade; communication, potable water, and utilities contained in blast-proof spaces; ventilation shafts for the parking garage in a secure area; and special security procedures to obtain access to the building's critical systems. The security enhancements made the office building suitable for all federal agencies with the exception of the United States Department of Defense. The 700,000-square-foot (65,000 m2) underground parking garage contains 1,500 spaces.

Several amenities were also added to the building. These included a 10,000-square-foot (930 m2), 400-seat auditorium on the courtyard/plaza level; a six-room, 11,000 square feet (1,000 m2) conference center which can accommodate meetings of 10 to 500 people; a full-service cafeteria on the plaza level, with access to the courtyard; and a fitness center for 100 people.

The exterior of the building was also radically changed. The celebrated key visual feature of the building, its exterior vertical white marble ribbing, was completely removed after it was found to be bowed from age and weather. Although this fundamentally changed the nature of Durrell's building, there was almost no public outcry. It was replaced by an energy-efficient, all-glass facade. Perhaps the most significant renovation feature was the structure's use of a chilled beam HVAC system, which uses chilled or heated water circulated in strategically placed columns in the interior space to cool and warm the building. To test the efficiency of the chilled beam technology, the system was installed in the penthouse of the building and tested for a full year. The architect agreed to use the system after the test outperformed specifications. The installation represented the first large-scale use of the chilled beam technology in the United States. Other energy-saving enhancements included motion and daylight detectors to turn lights off when not needed, and special exterior windows which automatically dim to prevent daytime heating. The building's ventilation system was also upgraded. The renovation left the structure with 1,400,000 square feet (130,000 m2) of interior space. The final cost of the renovation was pegged at \$250 million.

Some aesthetic improvements were made as well. The building now features a 1 acre (0.40 ha) park in its open-to-the-sky central courtyard. Most of the courtyard's concrete was removed and trees, shrubs, and flowers planted to absorb rainwater. The park, which is now no longer accessible by the public, also includes a very large granite abstract art sculpture ("Legacy") by Richard Deutsch. The sculpture is meant to reflect the original facade of the building by Edward Durrell Stone as well as the memory of David Nassif, Sr. and his son, David Nassif, Jr. The L'Enfant Plaza Metro station still has an entrance under the building on D Street SW (although this entrance closed between October 2007 and July 2008 for the building's reconstruction). The renovation installed artwork by internationally-known artist Stephen Knapp near this entrance, in which strong beams of light are passed through dyed glass to splay brightly colored patterns on the ceiling. The light sculpture, titled "Transformation", symbolizes the building's renovation and rebirth.

The Constitution Center is registered with the Green Building Council for Gold LEED Certification.

The renovated Constitution Center won two awards. The Mid-Atlantic Construction construction news Web site gave the building its "Project of the Year – Renovation/Restoration" accolade in December 2010. On March 25, 2011, the Washington Building Congress bestowed its 2011 WBC Craftsmanship Award on J.E. Richards, Inc. for excellence in workmanship in installing the power generation, distribution, and switchgear at Constitution Center.

In January 2011, Constitution Center was valued at \$446 million by city tax assessors, making it the third most valuable private property in the city that year.

## Tenants

The late-2000s recession left the renovated building struggling to find tenants. It was empty for nearly two years after it was opened for occupancy in April 2009. Both the United States Department of Homeland Security and NASA explored leasing all or part of it in 2009 and 2010, but chose not to do so. In August 2010, the United States Securities and Exchange Commission (SEC) signed a letter contract for 900,000 square feet (84,000 m2) of space at Constitution Center. The SEC planned to take occupancy in September 2011. In January 2011, the Office of the Comptroller of the Currency agreed to lease 640,000 square feet (59,000 m2) of space and the Federal Housing Finance Agency signed an agreement to occupy 335,000 square feet (31,100 m2) of space. The Office of the Comptroller and the Federal Housing Finance Agency both occupied the building by March 2012.

The SEC's occupancy of the building did not occur as planned. In October 2010, the SEC informed Nassif Associates that it needed only 340,000 square feet (32,000 m2) of the 900,000 square feet (84,000 m2) it had leased. On January 20, 2011, the SEC's inspector general launched an investigation into whether the SEC leased was proper and legal. SEC chairman Mary Schapiro was strongly criticized by Republicans in the United States House of Representatives for her handling of the lease, which she had personally approved. By May, it was unclear if the SEC would occupy any space at all in the building. On May 23, the SEC inspector general requested a formal opinion by the Comptroller General of the United States as to whether the lease violated the Antideficiency Act. The inspector general said SEC "grossly overestimated the amount of space needed at SEC Headquarters for the SEC's projected expansion by more than 300 percent and used these groundless and unsupportable figures to justify the SEC committing to an expenditure of \$556.8 million over 10 years".

In early July 2011, Nassif Associates said it had agreed to release the SEC from occupying 550,000 square feet (51,000 m2) of space at Constitution Center. The company asked the SEC to reimburse it for \$45 million in build-out and other expenses incurred between August 2010 and July 2011, but the agency declined to do so. Nassif Associates said it declined to file suit against the agency, although it indicated it would continue to negotiate with the SEC and other federal agencies to seek reimbursement. At the same time, the United States Department of Justice said it was considering whether to prosecute officials at the SEC over the lease's handling and the alleged forging of documents designed to justify it.

Occupancy issues at Constitution Center were further confused by legislative action. In October 2011, the United States House Committee on Transportation and Infrastructure voted 31-to-22 to permit the Federal Trade Commission to lease 160,000 square feet (15,000 m2) of space at Constitution Center and vacate the Apex Building (which would be turned over to the National Gallery of Art). Although this legislation was not adopted by Congress, the Transportation and Infrastructure Committee in March 2012 directed the General Services Administration (GSA) to analyze space needs for the Federal Trade Commission and several other federal agencies in the District of Columbia and issue a report to the committee on how Constitution Center could meet these needs. GSA reported in June 2012 that Constitution Center held too little space to house the entire FTC, and it was too costly to do so (after accounting for moving expenses and rental prices). GSA instead proposed that the FTC lease additional space at 601 New Jersey Avenue NW and 1800 M Street NW (where it already leased space, and where additional room was available).

In April 2012, Nassif Associates said the SEC owed it rent as well. The company said the letter contract required the agency to pay \$1.3 million a month beginning November 1, 2011. As of April 30, 2012, the agency owed \$7.75 million in back rent, a company spokesperson said. The agency disputed the cost, saying the build-out of the interior was never completed. SEC officials also said the agency now needed no space at all at Constitution Center, and that the SEC was working with GSA to find other federal tenants to take over its lease. In late May, the Federal Aviation Administration said it might lease 270,000 square feet (25,000 m2) of space in the building as part of a major consolidation of six of its offices in the city.

In July 2012, GSA bowed to congressional pressure and moved 1,100 FTC workers into Constitution Center from leased locations at 601 New Jersey Avenue NW and 1800 M Street NW. The deal kept the FTC in its Apex Building headquarters. Three months later, GSA rented out the last of its space in Constitution Center by signing leases for the National Endowment for the Arts and National Endowment for the Humanities.

## 2012 sale

On April 22, 2011, David Nassif Associates announced it was putting Constitution Center up for sale, and said it hoped to find a buyer by the end of summer 2011. The company also said it hoped for a \$900 million purchase price. Real estate banking firm Eastdil Secured assisted in securing a buyer.

In June 2012, the Washington Business Journal reported that CommonWealth Partners and Nassif Associates had negotiated a purchase agreement, but were unable to reach agreement. CommonWealth Partners then withdrew from any further discussions.

A deal for the sale of Constitution Center was agreed to in December 2012. MetLife and an unidentified investor (represented by Clarion Partners LLC) each purchased a 50 percent interest in the building. The sale price was \$734 million, or \$524 per square foot (0.093 square meters). The sale price was the most expensive in D.C. history for a single building. (It was not the most paid per square foot, however. That record went to two-building Market Square at 701 and 801 Pennsylvania Avenue NW, which sold in 2011 to Wells Real Estate Investment Trust for \$905 per square foot.) When the deal closed in February 2013, David Nassif Associates announced it would wind down its operations and liquidate its remaining obligations.

City tax assessors said that Constitution Center's value rose to \$725.8 million in 2014, up from \$573.5 million in 2013 (an increase of \$152.3 million), making it the most valuable taxable property in the District of Columbia.

Buildings and structures completed in 1969

Leadership in Energy and Environmental Design gold certified buildings

Skyscraper office buildings in Washington, D.C.


Genetic engineering

# 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. 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 US 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 first coined by Jack Williamson 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 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. 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.

In the 2007 video game, BioShock, genetic engineering plays an important role in the central storyline and universe. The game takes place in the fictional underwater dystopia Rapture, in which its inhabitants possess genetic superhuman abilities after injecting themselves with “plasmids”, a serum which grants such powers. Also in the city of Rapture are “Little Sisters”, little girls who are generically engineered, as well as a side-plot in which a cabaret singer sells her foetus to genetic scientists who implant false memories into the newborn and genetically engineer it to grow into an adult.

## See also

- Biological engineering
- Modifications (genetics)
- RNA editing#Therapeutic mRNA Editing
- Mutagenesis (molecular biology technique)

Manipulation of an organism's genome