Pusztai affair
Encyclopedia
The Pusztai affair is a controversy that began in 1998 after protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 scientist Arpad Pusztai
Árpád Pusztai
Árpád Pusztai is a Hungarian-born biochemist and nutritionist who spent 36 years at the Rowett Research Institute in Aberdeen, Scotland. He is a world expert on plant lectins, authoring 270 papers and three books on the subject...

 went public with research he was conducting with genetically modified potatoes. In a short interview he reported that rats fed potatoes engineered to express a plant lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...

 had stunted growth and a repressed immune system. This resulted in a media frenzy and Pusztai was suspended. Despite opposition from the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...

, the data was published in the academic journal The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

 in October 1999.

Background

Prior to 1995 no peer reviewed studies had been published investigating the safety of genetically modified food using human or animal feeding trials. In 1995 the Scottish Agriculture Environment and Fisheries Department commissioned a £1.6 million three year multi-centre research study to assess the safety of desiree red potatoes
Desiree potato
The Désirée is a red-skinned main crop potato originally bred in the Netherlands in 1962. It has yellow flesh with a distinctive flavour and is a favourite with allotment-holders because of its resistance to drought, although it is not well suited to organic growing...

 that had been genetically engineered
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...

 by biochemist John Gatehouse at Cambridge Agricultural Genetics (later renamed Axis Genetics). The potatoes had recently completed two years of field trials at Rothamsted Experimental Station
Rothamsted Experimental Station
The Rothamsted Experimental Station, one of the oldest agricultural research institutions in the world, is located at Harpenden in Hertfordshire, England. It is now known as Rothamsted Research...

. The Galanthus nivalis agglutinin (GNA) gene from the Galanthus (snowdrop) plant was inserted into the potato allowing the GNA lectin protein
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...

 to be synthesised
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...

. This lectin has been shown to be toxic to some insects.

Twenty-eight study proposals were presented with eight being chosen for peer review by the Biotechnology and Biological Sciences Research Council
Biotechnology and Biological Sciences Research Council
Biotechnology and Biological Sciences Research Council is a UK Research Council and NDPB and is the largest UK public funder of non-medical bioscience...

. The Rowett Research Institute
Rowett Research Institute
The Rowett Research Institute is a research centre for studies into food and nutrition located in Aberdeen, Scotland.-History:The institute was founded in 1913 when the University of Aberdeen and the North of Scotland College of Agriculture agreed that an "Institute for Research into Animal...

's proposals was chosen and a combined team of academics from the Scottish Crop Research Institute
Scottish Crop Research Institute
The Scottish Crop Research Institute more commonly known as the SCRI was a scientific institute located in Invergowrie near Dundee, Scotland. As of April 2011, when SCRI merged with the Macaulay Land Use Institute it is now part of The James Hutton Institute.-History:The institute was opened in...

, the Durham University Department of Biology
Durham University
The University of Durham, commonly known as Durham University, is a university in Durham, England. It was founded by Act of Parliament in 1832 and granted a Royal Charter in 1837...

 and the Rowett Institute was set up with Arpad Pusztai coordinating the study. Although the potatoes used were not a commercial variety and not intended for human consumption a contract was signed with Cambridge Agricultural Genetics, which included a profit-sharing agreement, if potatoes developed using this technology were approved and released commercially. This was the one of the first animal feeding studies conducted with genetically modified foods to be independently peer reviewed. Pusztai had previously studied the effect GNA had on rats in ten day feeding trials and concluded that it did not significantly affect the rats growth, although there was some hypertrophy
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...

 of the small intestine and a slight decrease of gut enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 activity.

The Experiment

The potatoes were chosen because they were deemed substantially equivalent
Substantial equivalence
Substantial equivalence is a concept, developed by OECD in 1991, that maintains that a novel food should be considered the same as and as safe as a conventional food if it demonstrates the same characteristics and composition as the conventional food. Substantial equivalence is important from a...

 to non-GM desiree red potatoes. The Rowett study aimed to examine the substantial equivalence of the modified potatoes and to test for any adverse effects on rats fed on the potatoes for ten days and three months. The study used two transgenic
Transgenesis
thumb|300px|right|A diagram comparing the genetic changes achieved through conventional plant breeding, transgenesis and cisgenesisTransgenesis is the process of introducing an exogenous gene – called a transgene – into a living organism so that the organism will exhibit a new property and transmit...

 lines of potato, both with the GNA gene inserted, and they were grown in the same conditions along with the non-GM parent plant. According to Pusztai the potatoes were not substantially equivalent, as one of the transgenic lines contained 20 percent less protein than the other and the starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...

 and sugar contents varied by up to 20%. It was also found that neither of the two GM lines were substantially equivalent to their non-GM parent. In Pusztai's opinion the lack of substantial equivalence was reason enough to discontinue any further experimentation with the potatoes.

Rats were fed on raw and cooked genetically modified potatoes, using unmodified Desiree Red potatoes as controls
Scientific control
Scientific control allows for comparisons of concepts. It is a part of the scientific method. Scientific control is often used in discussion of natural experiments. For instance, during drug testing, scientists will try to control two groups to keep them as identical and normal as possible, then...

. One of the controls consited of an unmodified Desiree Red potato spiked with the GNA snowdrop lectin. Twelve feeding experiments were conducted, ten short-term (10 days) and two long-term (110 days). Before the experiment Pusztai and his team say they expected there to be no differences between the rats fed modified potatoes when compared to rats fed the non-modified ones. Their experiment however showed a statistically significant difference in the thickness of the stomach mucosa. The mucosa of rats fed raw or cooked potato modified with the GNA gene was thicker than that of rats fed the unmodified potato. The crypt
Crypt (anatomy)
Crypts are anatomical structures that are narrow but deep invaginations into a larger structure.One common type of anatomical crypt is the Crypts of Lieberkühn. However, it is not the only type: some types of tonsils also have crypts...

 length in the jejunum
Jejunum
The jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...

 was greater on rats fed the raw modified potato, although there was no statistical difference observed in the rats fed the cooked potato. As these effects were not observed in rats fed the control potatoes spiked with GNA, Pusztai concluded that the differences were not due to the presence of GNA, but were a result of transformation procedure. Stanley Ewen, who collaborated with Pusztai on the experiment, said that the use of the cauliflower mosaic virus
Cauliflower mosaic virus
Cauliflower mosaic virus is the type member of the caulimoviruses, one of the six genera in the Caulimoviridae family, pararetroviruses that infect plants...

 as a promoter could be the likely cause of the changes observed.

Announcement

On June 22, 1998 Pusztai revealed his research findings during an interview on Granada Television
Granada Television
Granada Television is the ITV contractor for North West England. Based in Manchester since its inception, it is the only surviving original ITA franchisee from 1954 and is ITV's most successful....

's current affairs programme World in Action
World in Action
World in Action was a British investigative current affairs programme made by Granada Television from 1963 until 1998. Its campaigning journalism frequently had a major impact on events of the day. Its production teams often took audacious risks and gained a solid reputation for its often...

titled "Eat up your genes". He was given permission to do the interview by Rowett Institute Director Philip James and their press officer was present at the start of filming. During the interview Puzstai said that he had "concerns that some of the testing techniques are not up to what we thought it was necessary to do, and therefore we should have more testing." When asked why he felt concerned he said "it was because we had done some experiments which made us feel concerned" and discussed his results with the programme in general terms based on his experiences. At the time he said he was not sure if he should reveal results from experiments that had not been completed and did not think that the programme would be hostile towards genetically modified food. At the time of the interview he estimated that the experiments were 99 percent complete.

The show aired seven weeks later on Monday August 10, with the Pusztai interview lasting 150 seconds. On the show he said that rats in his experiments suffered stunted growth and had suppressed immune systems and that more safety research was required. He also said that "If you gave me the choice now, I wouldn't eat it" and it was "very, very unfair to use our fellow citizens as guinea pigs. A press release from World in Action was issued the day before the broadcast, resulting in Pusztai and the Rowett Institute receiving numerous phone calls from government, industrial, NGO and media organisations. James says he was dismayed that unpublished data had been released and withdrew Pusztai from any further media commitments on Monday morning. He eventually ended up suspending Pusztai, used misconduct procedures to seize his data, banned him from speaking publically and did not renew his annual contract.

Investigative journalist Andrew Rowell wrote in his book Don't worry, it's safe to eat: The true story of GM food, BSE and foot and mouth that pressure to sack Pusztai had been applied to the institute from Monsanto, a multinational company that owns 90 percent of GM seed technology. According to Rowell professor Robert Orskov, who was working at Rowett at the time, heard that Clinton rang Blair who then rang James to tell him to silence Pusztai. Pusztai's colleague Stanley Ewen says he heard the story from another Rowett researcher, Asim Duttaroy. In 2008 James Randerson, The Guardian
The Guardian
The Guardian, formerly known as The Manchester Guardian , is a British national daily newspaper in the Berliner format...

's environment and science news editor, telephoned Orskov and Duttaroy and emailed James. Orskov said that while he would not be surprised if the calls had occurred, he had no personal knowledge of them and Duttaroy remembers his conversation with Ewen, but not making any statements about political manipulation. In 1999 James had denied receiving any phone calls from Government
Government of the United Kingdom
Her Majesty's Government is the central government of the United Kingdom of Great Britain and Northern Ireland. The Government is led by the Prime Minister, who selects all the remaining Ministers...

 or Cabinet
Cabinet of the United Kingdom
The Cabinet of the United Kingdom is the collective decision-making body of Her Majesty's Government in the United Kingdom, composed of the Prime Minister and some 22 Cabinet Ministers, the most senior of the government ministers....

, but later admitted to Randerson that he was phoned by the Scottish Office of Agriculture
Scottish Office
The Scottish Office was a department of the United Kingdom Government from 1885 until 1999, exercising a wide range of government functions in relation to Scotland under the control of the Secretary of State for Scotland...

. He says it was with the scientific officer and had taken place after he had already made the decision to suspend Pusztai.

At the time there was confusion over just what experiments had been conducted. The media initially reported that there were two lines of genetically modified potatoes. In his interview Pusztai had mentioned two lines, meaning the two GNA lines. The Rowett institute mistakenly assumed the media was talking about a second line transformed with concanavalin A
Concanavalin A
Concanavalin A is a lectin originally extracted from the jack-bean, Canavalia ensiformis. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups...

 (ConA), a Jack Bean
Canavalia
Canavalia is a genus of flowering plants in the legume family and comprises approximately 70-75 species of tropical vines. Members of the genus are commonly known as jack-beans. The species of Canavalia endemic to the Hawaiian Islands were named āwikiwiki by the Native Hawaiians...

 lectin which is toxic to mammals. Transgenic ConA Potatoes had been developed, but they had never been tested. Two press releases issued by the Rowett Institute on the 10th and 11th praised Pusztais research and supported increased safety tests on genetically modified food. They also said that the potatoes were modified with ConA, adding to the confusion. Pusztai says he never saw the press release before it went out, so had no opportunity to correct the mistake. James says that he drafted it and Pusztai rewrote a whole section, but did not see the final copy. The mistaken belief that the ConA gene was inserted into the potato led scientist Sir Robert May
Robert May, Baron May of Oxford
Robert McCredie May, Baron May of Oxford, OM, AC, PRS is an Australian scientist who has been Chief Scientific Adviser to the UK Government, President of the Royal Society, and a Professor at Sydney and Princeton. He now holds joint professorships at Oxford, and Imperial College London...

 and Agricultural Minister Jack Cunningham
Jack Cunningham
John "Jack" Anderson Cunningham, Baron Cunningham of Felling, PC, DL is a British Labour Party politician, who was the Member of Parliament for Copeland from 1983 to 2005, and previously served in the Cabinet.-Early life:...

 to release statements to the media saying that the findings were not surprising as a known poison had been added to the potato and some GM scientists still dismiss Pusztai's work due to this.

An audit of Pusztais work was conducted by the Rowett Institute in October and it concluded that the data did not support his conclusions.
In February 1999, 22 international scientists from 13 countries, organised by the environmental group Friends of the Earth
Friends of the Earth
Friends of the Earth International is an international network of environmental organizations in 76 countries.FOEI is assisted by a small secretariat which provides support for the network and its agreed major campaigns...

, published a memo responding to the audit. It says that their independent examination of the data supports Pusztai's conclusions and he had a right to be concerned by his findings. On 19 February the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...

 publicly announced that a committee would review his work. World in action reporters Laurie Flynn and Michael Sean Gillard say that this was an unusual step as the Royal Society does not normally conduct peer reviews. The data was sent to six anonymous reviewers and the resulting review was published in June. It stated that Pusztai's experiments were poorly designed, contained uncertainties in the composition of diets, did not have a large enough number of rats, used incorrect statistical methods and lacked consistency within experiments. Puzstai responded by saying they only reviewed internal Rowett reports, which did not include the design of the experiments or methodology used.

Publishing

Pusztai's experiment, co-authored by Stanley Ewen, was eventually published in 1999 as a letter in The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

. Due to the controversial nature of his research the letter was reviewed by six reviewers - three times the usual number. One, John Pickett of the government funded Institute of Arable Crops Research, publicly opposed the letter; another thought it was flawed, but wanted it published "to avoid suspicions of a conspiracy against Pusztai and to give colleagues a chance to see the data for themselves". The other four raised questions that were addressed by the authors. After consulting with the Royal Society, Pickett publicly attacked the Lancet for agreeing to publish the study. The letter - which used data held by Dr Ewen and so was not subject to James veto on Pusztai's work - reported significant
Statistical significance
In statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....

 differences between the thickness of the gut epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 of rats fed genetically modified potatoes, compared to those fed the control diet.

After publishing it was criticised on the grounds that the unmodified potatoes were not a fair control diet and that any rats fed only on potatoes will suffer from a protein deficiency. Pusztai responded to these criticisms by stating that all the diets had the same protein and energy content and that the animals were pair-fed, meaning they were given the same amount of food. In an interview, Pickett later stated that Richard Horton (the Lancet editor) had a political motive for publishing the paper, because the "referees" had rejected it. According to Pusztai this claim was repeated by academic critics who assumed that Pickett's use of the plural suggested that the study had failed peer review.

Horton says he received a "very aggressive" phone call calling him "immoral" and threatening him that if he published the paper it would "have implications for his personal position" as editor. Peter Lachmann
Peter Lachmann
Professor Sir Peter Julius Lachmann, ScD, FRS, FMedSci is a British immunologist, specifically a complementologist. He is emeritus Sheila Joan Smith Professor of Immunology at Cambridge University, a fellow of Christ's College, Cambridge and honorary fellow of Trinity College, Cambridge and of...

, the former vice-president and biological secretary of the Royal Society and president of the Academy of Medical Sciences, admits making the call but denies that he threatened Horton and says the call was to "discuss his error of judgment" in publishing the letter. Following publication, co author Dr Stanley Ewen, says he found his career options "blocked at a very high level" and retired. He has also conducted a followup study further investigating Pusztai's work and presented the work to a lectin meeting in Sweden.

In 2005 Pusztai was given a whistleblower
Whistleblower
A whistleblower is a person who tells the public or someone in authority about alleged dishonest or illegal activities occurring in a government department, a public or private organization, or a company...

 award from the Federation of German Scientists.

External links

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