About Authors:
Satyanand Tyagi1*, Patel Chirag J1, Patel Jaimin1, Chaudhari Bharat1, Ram Narayan Prajapati3
1*President, Tyagi Pharmacy Association & Scientific Writer (Pharmacy),
Chattarpur, New Delhi, India-110074.
Prof. Satyanand Tyagi is a life time member of various pharmacy professional bodies like IPA, APTI and IPGA. He has published various research papers, review articles and short communications. He is member of Editorial Advisory Board for some reputed Pharmacy Journals. He is recently appointed as an Author for International Pharmaceutical Writers Association (IPWA). (Appointed as an author for the chapters of book on Pharmaceutical Chemistry). His academic work includes 62 Publications (52 Review Articles, 08 Research Articles and 02 short Communications of Pharmaceutical, Medicinal and Clinical Importance, published in standard and reputed National and International Pharmacy journals; Out of 62 publications, 11 are International Publications). His research topics of interest are neurodegenerative disorders, diabetes mellitus, cancer, rare genetic disorders, psycho-pharmacological agents as well as epilepsy.
2Department of Pharmaceutics, Maharishi Arvind Institute of Pharmacy, Mansarovar, Jaipur, Rajasthan, India-302020.
3Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India-284128.
*sntyagi9@yahoo.com, +91-9871111375/09582025220
ABSTRACT:
A Genetically Modified (GM) tomato, or transgenic tomato or genetically engineered is a tomato that has had its genes modified, using genetic engineering. The first commercially available genetically modified food was a tomato engineered to have a longer shelf life. Currently there are no genetically modified tomatoes available commercially, but scientists are developing tomatoes with new traits like increased resistance to pests or environmental stresses. Other projects aim to enrich tomatoes with substances that may offer health benefits or be more nutritious.
As well as aiming to produce novel crops, scientists produce genetically modified tomatoes to understand the function of genes naturally present in tomatoes.A new type of tomato has developed by scientists in the UK and other European countries in which a purple tomato has been created. This tomato in a pilot test significantly extended the life span of cancer-susceptible mice that were fed the new tomatoes compared to mice that were fed normal tomatoes. The team of scientists have taken genes from the snapdragon plant, inserted them into the tomato plants, and heave created purple tomatoes which are high in anthocyanin. These pigments occur naturally at high levels in berry fruits such as the blackberry, cranberry and blueberry. These are more commonly known as antioxidants and they protect against some cancers, cardiovascular disease, age-related degenerative diseases, diabetes, obesity and other illnesses. The truth is most people who develop these illnesses don’t eat enough fruit. Certain fruits have chemical which can protect the body against cancer, cardiovascular disorders, and other degenerative diseases. European scientists report that they have made a purple tomato that significantly extended the life span of cancer-prone mice. Anthocyanin has high antioxidant activity and it also modulates cellular signaling pathways in ways that promote health. The researchers chose to enhance tomatoes because they are a popular food crop and can be easily incorporated into a variety of meals. Modifying tomatoes initially improved skin. Incorporating a higher dosage of anthocyanin into the tomato could change results of its effects on humans quite significantly.
The aim of present article is to enumerate the health benefits of these Genetically Modified (GM) tomatoes. An attempt is also made to focus on drawbacks or disadvantages of GM tomatoes.
Reference Id: PHARMATUTOR-ART-1536
INTRODUCTION
A genetically modified tomato, or transgenic tomato (Fig. 1) is a tomato that has had its genes modified, using genetic engineering. The first commercially available genetically modified food was a tomato engineered to have a longer shelf life (the Flavr Savr). Currently there are no genetically modified tomatoes available commercially, but scientists are developing tomatoes with new traits like increased resistance to pests or environmental stresses. Other projects aim to enrich tomatoes with substances that may offer health benefits or be more nutritious. As well as aiming to produce novel crops, scientists produce genetically modified tomatoes to understand the function of genes naturally present in tomatoes. The tomato originated from South America and was brought to Europe by the Spanish in the 16th century [1]. Wild tomatoes are small, green and largely unappetizing, but after centuries of breeding there are now thousands of varieties grown worldwide.
Agro bacterium-mediated genetic engineering techniques were developed in the late 1980s that could successfully transfer genetic material into the nuclear genome of tomatoes [2].Genetic material can also be inserted into a tomato cell's chloroplast and chromoplast plastomesusing biolistics. Tomatoes were the first food crop with an edible fruit where this was possible [3]. Agrobacerium tumefaciens is and excellent species of soil dwelling bacteria that can infect plants with a piece of its own DNA. Agro bacterium mediated transformation is an effective and widely used approach to introduce foreign DNA into dicotyledons plants [4]. The DNA gets a hold of the plant cellular machinery and uses it to ensure the proliferation of bacterial population. The advantage of this gene is that insecticidal toxin genes or other various herbicides can be engineered in the bacterial DNA. This bacterium shortens the plant breeding process. Most of all, it allows new genes to engineered into crops [5]. The tomato has been a symbol for genetically modified food for many years. In 1994, genetically modified tomatoes hit the market in the US as the first commercially available genetically modified crop. GM tomatoes have since disappeared. This transgenic tomato (FlavrSavr) had a "deactivated" gene (Antisense approach).
This meant that the tomato plant was no longer able to produce polygalacturonase, an enzyme involved in fruit softening. The premise was that tomatoes could be left to ripen on the vine and still have a long shelf life, thus allowing them to develop their full flavor. Normally, tomatoes are picked well before they are ripe and are then ripened artificially. These GM tomatoes, however, did not meet their expectations. Although they were approved in the US and several other countries, tomatoes with delayed ripening have disappeared from the market after peaking in 1998. At this point, no genetically modified tomatoes are being grown commercially in North America or in Europe. Genetically modified tomatoes are not approved in Europe. Applications that were submitted several years ago have since been withdrawn. Tomato puree made from GM tomatoes was a big success in the mid 90s in Great Britain. The fact that the tomatoes were of GM origin was clearly stated on the label. Later, an application was submitted for approval according to EU laws on genetic engineering. Although EU committees of scientific experts assessed the tomato puree as harmless, Member States could not come to an agreement. The application was withdrawn in 2002. Scientists are still working with genetic tools to give tomatoes new traits like resistance to insect pests and fungal and viral pathogens.
Other projects aim to enrich tomatoes with substances offering health benefits. All of these products, however, are still many steps away from receiving authorisation.
Figure 1: A View of Genetically Engineered Tomatoes
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ILLUSTRATIVE EXAMPLES AND PRACTICAL APPLICATIONS OF GENETICALLY MODIFIED TOMATOES
* Delayed Ripening:
Tomatoes have been used as a model organism to study the fruit ripening of climacteric fruit. To understand the mechanisms involved in the process of ripening, scientists have genetically engineered tomatoes [6].
In 1994, the Flavr Savr became the first commercially grown genetically engineered food to be granted a license for human consumption. A second copy of the tomato genepolygalacturonase was inserted into the tomato genome in the antisense direction [7]. The polygalacturonase enzyme degrades pectin, a component of the tomato cell wall, causing the fruit to soften. When the antisense gene is expressed it interferes with the production of the polygalacturonase enzyme, delaying the ripening process. The Flavr Savr failed to achieve commercial success and was withdrawn from the market in 1997. Similar technology, but using a truncated version of the polygalacturonase gene, was used to make a tomato. DNA Plant Technology (DNAP), Agritope and Monsanto developed tomatoes that delayed ripening by preventing the production of ethylene, a hormone that triggers ripening of fruit.
All three tomatoes inhibited ethylene production by reducing the amount of 1-aminocyclopropane-1-carboxylic acid (ACC), the precursor to ethylene. DNAP's tomato, called Endless Summer, inserted a truncated version of the ACC synthase gene into the tomato that interfered with the endogenous ACC synthase. Monsanto's tomato was engineered with the ACC deaminase gene from the soil bacterium Pseudomonas chlororaphis that lowered ethylene levels by breaking down ACC [8]. Agritope introduced an S-adenosylmethionine hydrolase (SAMase) encoding gene derived from the E. coli bacteriophage T3, which reduced the levels of S-adenosylmethionine, a precursor to ACC [9]. Endless summer was briefly tested in the marketplace, but patent arguments forced its withdrawal [10]. Scientists in India have delayed the ripening of tomatoes by silencing two genes encoding N-glycoprotein modifying enzymes, α-mannosidase and β-D-N-acetylhexosaminidase. The fruits produced were not visibly damaged after being stored at room temperature for 45 days, whereas unmodified tomatoes had gone rotten [11]. In India, where 30% of fruit is wasted before it reaches the market due to a lack of refrigeration and poor road infrastructure, the researchers hope genetic engineering of the tomato may decrease wastage.
* Environmental Stress Tolerance:
Abiotic stresses like frost, drought and increased salinity are a limiting factor to the growth of tomatoes [12]. While no genetically modified stress tolerant plants are currently commercialized, transgenic approaches have been researched. An early tomato was developed that contained an antifreeze gene (afa3) from the winter flounder with the aim of increasing the tomato's tolerance to frost (see Fish tomato). The antifreeze protein was found to inhibit ice recrystallization in the flounder’s blood, but had no effect when expressed in transgenic tobacco [13].
The resulting tomato was never commercialized, but raised ethical questions over adding genes from one kingdom to another [14]. Other genes from various species have been inserted into the tomato with the hope of increasing their resistance to various environmental factors. A gene from rice (Osmyb4), which codes for a transcription factor, that was shown to increase cold and drought tolerance in transgenic Arabidopsis thaliana plants was inserted into the tomato. This resulted in increased drought tolerance, but did not appear to have any effect on cold tolerance [15]. Over expressing a vacuolar Na+/H+ antiport (AtNHX1) from A. thaliana lead to salt accumulating in the leaves of the plants, but not in the fruit and allowed them to grow more in salt solutions than wildtype plants [16]. They were the first salt-tolerant, edible plants ever created. Tobacco osmotic genes over expressed in tomatoes produced plants that held higher water content than wild type plants increasing tolerance to drought and salt stress [17].
* Pest Resistance:
The insecticidal toxin from the bacterium Bacillus thuringiensis has been inserted into a tomato plant [18]. When field tested they showed resistance to the tobacco hornworm (Manduca sexta), tomato fruit worm (Heliothis zea), the tomato pinworm (Keiferia lycopersicella) and the tomato fruit borer (Helicoverpa armigera) [19, 20]. A 91 day feeding trail in rats showed no adverse effects, but the Bt tomato has never been commercialized. Tomatoes resistant to a root knot nematode have been created by inserting a cysteine proteinase inhibitor gene from taro. A chemically synthesized ceropin B gene, usually found in the giant silk moth (Hyalophora cecropia), has been introduced into tomato plants and vivo studies show significant resistance to bacterial wilt and bacterial spot. When the cell wall proteins, polygalacturonase and expansin are prevented from being produced in fruits, they are less susceptible to the fungus Botrytis cinerea than normal tomatoes [21].
* Improved Nutrition
Tomatoes have been altered in attempts to improve their flavor or nutritional content. In 2000, the concentration of pro-vitamin A was increased by adding a bacterial gene encodingphytoene desaturase, although the total amount of carotenoids remained equal [22]. The researchers admitted at the time that it had no prospect of being grown commercially due to the anti-GM climate. Sue Meyer of the pressure group Gene watch, told The Independent that she believed, "If you change the basic biochemistry, you could alter the levels of other nutrients very important for health". More recently, scientists have increased the production of anthocyanin, an antioxidant in tomatoes in several ways.
One group added a transcription for the production of anthocyanin from Arabidopsis thaliana [23], whereas another used transcription factors from snapdragon (Antirrhinum) When the snapdragon genes where used, the fruits had similar anthocyanin concentrations to blackberries and blueberries, and when fed to cancer susceptible mice, extended their life span[24]. Another group has tried to increase the levels of isoflavone, known for its potential cancer preventative properties, by introducing the soybean isoflavone synthase into tomatoes [25].
* Improved Taste
When geraniol synthase from lemon basil (Ocimum basilicum) was expressed in tomato fruits under a fruit-specific promoter, 60% of untrained taste testers preferred the taste and smell of the transgenic tomatoes.
The fruits contained around half the amount of lycopene, reducing the health benefits of eating them [26].
* Vaccines
Tomatoes (along with potatoes, bananas and other plants) are being investigated as vehicles for delivering edible vaccines. Clinical trials have been conducted on mice using tomatoes expressing antibodies or proteins that stimulate antibody production targeted to norovirus, hepatitis B, rabies, HIV, anthrax and respiratory syncytial virus [27]. Korean scientists are looking at using the tomato to expressing a vaccine against Alzheimer's disease [28]. Hilary Koprowski, who was involved in the development of the polio vaccine, is leading a group of researchers in developing a tomato expressing a recombinant vaccine to SARS [29].
MOST RECENT DEVELOPMENTS AND BASIC RESEARCH
A new type of tomato has developed by scientists in the UK and other European countries in which a purple tomato has been created. This tomato in a pilot test significantly extended the life span of cancer-susceptible mice that were fed the new tomatoes compared to mice that were fed normal tomatoes. The team of scientists have taken genes from the snapdragon plant, inserted them into the tomato plants, and heave created purple tomatoes which are high in anthocyanin. These pigments occur naturally at high levels in berry fruits such as the blackberry, cranberry and blueberry. These are more commonly known as antioxidants and they protect against some cancers, cardiovascular disease, age-related degenerative diseases, diabetes, obesity and other illnesses.
The truth is most people who develop these illnesses don’t eat enough fruit. Certain fruits have chemical which can protect the body against cancer, cardiovascular disorders, and other degenerative diseases. European scientists report that they have made a purple tomato that significantly extended the life span of cancer-prone mice. Anthocyanin has high antioxidant activity and it also modulates cellular signaling pathways in ways that promote health. The researchers chose to enhance tomatoes because they are a popular food crop and can be easily incorporated into a variety of meals. Modifying tomatoes initially improved skin [30]. Incorporating a higher dosage of anthocyanin into the tomato could change results of its effects on humans quite significantly. Researchers did this by engineering tomatoes to express two genes that normally promote the biosynthesis of anthocyanin in snapdragons (the Delila and Rosea1 genes) [31].
The engineered tomatoes contained anthocyanin throughout the entire fruit at levels comparable to blueberries and blackberries (2.83 mg of anthocyanins per gram of tomato). Anthocyanins are chemicals called flavonoids which clean up potentially harmful oxygen molecules in the body. Although they are produced naturally by tomato plants, they are normally found only in the leaves. As a result of anthocyanin, the tomatoes become purple at its last stage of the ripening process. The newly inserted genes were passed on to future generations of tomatoes, lasting through five generations as of the time the paper was prepared. Mice lacking p53 develop a variety of cancers at an early age and have an average life span of 142 days, and they live a maximum of 211 days. A diet consisting of modified purple tomatoes extended the life span of these mice to an average 182.2 days; some mice lived up to 260 days. Regular tomatoes had no effect on the average life span. The addition of higher levels of anthocyanin and the lycopene which is already contained within the tomato is very beneficial to cancer patients.
British scientists behind the crop believe their purple tomato is the respectable face of genetic modification and could help convince the public of the benefits of GM food. The purpose of developing a new kind of tomato is to help people consume in their daily meal, as compared to antioxidants from berries which aren’t consumed as much. Tomatoes are used as a model organism in scientific research and they are frequently genetically modified to further our understanding of particular processes. Tomatoes have been used as a model in map-based cloning, where transgenic plants must be created to prove that a gene has been successfully isolated [32]. The plant peptide hormone, systemin was first identified in tomato plants and genetic modification has been used to demonstrate its function, by adding antisense genes to silence the native gene, or by adding extra copies of the native gene [33, 34].
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NEWER RESEARCH RELATED TO GENETICALLY ENGINEERED TOMATOES
For the first time, genetically engineered tomato plants produced a peptide that mimics the actions of good cholesterol when eaten, researchers reported at the American Heart Association's Scientific Sessions 2012.In the study, mice that ate the freeze-dried, ground tomatoes had less inflammation and reduced atherosclerosis (plaque build-up in the arteries). "We have found a new and practical way to make a peptide that acts like the main protein in good cholesterol, but is many times more effective and can be delivered by eating the plant," said Alan M [35].
Fogelman, M.D., senior author of the study and executive chair of the Department of Medicine and director of the Atherosclerosis Research Unit in the David Geffen School of Medicine at UCLA. Researchers genetically engineered the tomatoes to produce 6F, a small peptide that mimics the action of ApoA-1, the chief protein in high density lipoprotein (HDL or "good" cholesterol). They fed the tomatoes to mice that lack the ability to remove low density lipoprotein (LDL or "bad" cholesterol) from their blood and readily develop inflammation and atherosclerosis when consuming a high-fat diet.
After the mice ate the tomatoes as 2.2 percent of their Western-style high-fat, calorie-packed diet, those given the peptide-enhanced tomatoes had significantly:
*lower blood levels of inflammation;
*higher paraoxonase activity, an anti-oxidant enzyme associated with good cholesterol and related to a lower risk of heart disease;
*higher levels of good cholesterol;
*decreased lysophosphatidic acid, a tumour promoter that accelerates plaque build-up in arteries in animal models; and
*less atherosclerotic plaque.
"To our knowledge this is the first example of a drug with these properties that has been produced in an edible plant and is biologically active when fed without any isolation or purification of the drug," Fogelman said.
DISCUSSION AND CONCLUSION
Many people eat genetically modified food without knowing it. But the question is genetically foods safe for human consumption changed? Many of the foods we buy at the market of genetically modified ingredients. The most common genetically modified foods are derived from plants – soybeans, corn, canola and cotton seeds. So many foods obtained by the knowledge that, like cereal, snack, consisting of soybean, cotton and canola can be used genetically engineered components. Also, genetically modified tomatoes and potatoes.What are genetically modified foods? It is safe to consume for us? Also, transgenic foods or genetically altered known refers to foods that have their DNA altered through genetic engineering. The plants are modified in the laboratory in order to improve their desirable properties and nutritional value. Here are some of the pros and cons of genetically modified foods:
The disadvantages [36] are:
*Health caused by the artificial food
*To provide the contamination of food and water through the use of chemicals on plants
*The creation of herbicide-resistant weeds
*Loss of biodiversity in crops
*The disruption of ecological balance
The advantages, but a few,
*Resistance to pests and diseases
*Increased food supply
Today in Nature Biotechnology, European scientists report that they have made a purple tomato that significantly extended the life span of cancer-prone mice. The scientists were interested in anthocyanins, bioactive chemicals that are found in high concentrations in blackberries and blueberries. Many research groups have determined that these chemicals have high antioxidant activities and modulate cellular signalling pathways in ways that promote health. The researchers chose to enhance tomatoes, as they are a popular food crop and can be easily incorporated into a variety of meals.
Tomatoes already contain very small amounts of flavonoids like anthocyanins, so it should be straightforward to give them a boost.Previous attempts to modify tomatoes only managed to improve the contents of the skin, which makes up very little of the fruit. To get a more dramatic enhancement, the whole fruit would need to contain high levels of anthocyanins. The researchers were able to accomplish this by engineering tomatoes to express two genes that normally promote the biosynthesis of anthocyanins in snapdragons (the Delila and Rosea1 genes). Do these engineered tomatoes work when they're incorporated into the actual diet of living animals? They seem to help mice that lack a gene (p53) that is damaged in about half of the cancers in humans. Mice lacking p53 develop a variety of cancers at an early age and have an average life span of 142 days, and they live a maximum of 211 days. A diet consisting of modified purple tomatoes extended the life span of these mice to an average 182.2 days; some mice lived up to 260 days. Regular tomatoes had no affect on the average life span. It certainly seems that a diet consisting of foods with high levels of anthocyanins has significant health benefits. Scientists are now attempting to determine if we need to consume anthocyanins that naturally occur in fruits and vegetables, or if we can just ingest them alone to get their benefits. Even if we end up being able to take bioactive compounds in a pill, it might be more fun and appetizing to decorate salads, sandwiches, and pasta with purple tomatoes [37, 38].
ACKNOWLEDGEMENT
As a corresponding author, My Self, Satyanand tyagi is highly thankful to my Parents and Teachers for their moral support and encouragement. Last but not the least, thanks to Lord Shiva for showering his blessings best owned on me.
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