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Some interesting facts: ³

GM tomatoes: The first and only safety evaluation of a GM crop, the FLAVR SAVR^TM tomato, was commissioned by Calgene, as required by the FDA. This GM tomato was produced by inserting kanr genes into a tomato by an ‘antisense’ GM method. The test has not been peer-reviewed or published but is on the internet. The results claim there were no significant alterations in total protein, vitamins and mineral contents and in toxic glycoalkaloids. Therefore, the GM and parent tomatoes were deemed to be “substantially equivalent.”

In acute toxicity studies with male/female rats, which were tube-fed homogenized GM tomatoes, toxic effects were claimed to be absent. However: Some rats died within a few weeks after eating GM tomatoes.

• The unacceptably wide range of rat starting weights (±18% to ±23%) invalidated these findings.
• No histology on the intestines was done even though stomach sections showed mild/moderate erosive/necrotic lesions in up to seven out of twenty female rats but none in the controls. However, these were considered to be of no importance, although in humans they could lead to life-endangering hemorrhage, particularly in the elderly who use aspirin to prevent thrombosis.
• Seven out of forty rats on GM tomatoes died within two weeks for unstated reasons.
• These studies were poorly designed and therefore the conclusion that FLAVR SAVR^TM tomatoes were safe does not rest on good science, questioning the validity of the FDA’s decision that no toxicological testing of other GM foods will in future be required.

GM maize: Two lines of Chardon LL herbicide-resistant GM maize expressing the gene of Phosphinothricin Acetyltransferase Enzyme (PAT-PROTEIN) before and after ensiling showed significant differences in fat and carbohydrate contents compared with non-GM maize and were therefore substantially different. Toxicity tests were only performed with the PAT-PROTEIN even though with this the unpredictable effects of the gene transfer or the vector or gene insertion could not be demonstrated or excluded. The design of these experiments was also flawed because:

Rats’ ability to digest was decreased after eating GM corn.

• The starting weight of the rats varied by more than ±20% and individual feed intakes were not monitored.
• Feed conversion efficiency on PAT-PROTEIN was significantly reduced.
• Urine output increased and several clinical parameters were also different.
• The weight and histology of the digestive tract (and pancreas) was not measured.

Thus, GM maize expressing PAT-PROTEIN may present unacceptable health risks.

GM soybeans: To make soybeans herbicide resistant, the gene of 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacterium was used. Safety tests claim the GM variety to be “substantially equivalent” to conventional soybeans. The same was claimed for GTS (glyphosate-resistant soybeans) sprayed with this herbicide.¹¹ However, several significant differences between the GM and control lines were recorded¹⁰ and the statistical method used was flawed because:

• Instead of comparing the amounts of components in a large number of samples of each individual GTS with its appropriate parent line grown side-by-side and harvested at the same time, the authors compared samples from different locations and harvest times.
• There were also differences in the contents of natural isoflavones (genistein, etc.) with potential importance for health.
• Additionally, the trypsin inhibitor (a major allergen) content was significantly increased in GTS.

Because of this, and the large variability (± 10% or more), the lines could not be regarded as “substantially equivalent.”

GM potatoes: There is only one peer-reviewed publication on GM potatoes that express the soybean glycinin gene. However, the expression level was very low and no improvements in the protein content or amino acid profile were obtained.

The Bt- Brinjal debate continues to occupy center-stage in India as the series of common- platform debates on the safety of the crop reached Bangalore. Minister Jayaram Ramesh was once again ‘gheraoed’ (surrounded) by angry and agitated farmers, social and environmental activists in the garden city. The activists more or less forced the minister to take a decision on the matter by February 10, which is just 3 days away. While the minister sticks to his assurances that his decision will be guided by sound science and public good, it seems a Herculean task to be undertaken given the sharp divide over this issue both in political and agricultural circles. In any case, this will be a decision worth watching out for. As the minister himself says, ‘the decision will disappoint half of India while the rest will be happy’.

Meanwhile, Andhra Pradesh joined the long list of States opposing the cultivation of this controversial crop. The southern state in India from which minister J. Ramesh is himself an MP joined West Bengal, Bihar, Orissa, Kerala, Karnataka, Madhya Pradesh and Chhattisgarh in their veto of Bt-Brinjal cultivation.

Another development is the statement issued by AP agriculture minister N Raghuveera Reddy at a press conference in Hyderabad on Saturday evening saying that a committee appointed by it had concluded that further trials and a deeper study is needed before going for the commercialization of Bt-Brinjal “There is a need for scientific approval before the crop is commercially produced. We are not against technology improvements in the agriculture field, but we want to ensure that the technology benefits the farmer and increases the yield. We had supported Bt cotton earlier but we are convinced that Bt Brinjal is not yet ready for commercial cultivation. The decision was taken after close consultations with scientists,” he said ¹ .

What still troubles me in all this hullabaloo, is the overwhelming (as I see it !!) data and opinions expressed by eminent experts and scientists in the field of Agriculture, that has been brought in public domain and has been equally scrupulously ignored by the regulatory agencies of this country. The fact that science and scientists in India work under political pressure is a known fact and this was further underlined by experts at a panel meeting organized by the People’s Science Forum to in the backdrop of the Bt-Brinjal issue. The meet was held in Chandigarh last week and had speakers such as Dr V C Nanda, former head, Department of Advanced Mathematics. In context of the Bt problem he said, The American Academy of Environment Medicine has said that there should be a moratorium on genetically modified (GM) food. Doctors are also not prepared to treat patients with GM-induced symptoms. Two Texan scientists have found that GM crop seeds are poisonous and should not be included in fodder, but in India there is no check.”² The panelists further alleged that frauds were being committed by companies such as Mahyco- Monsanto in an attempt to pass off the new technology.

When I trawled the net for reports on toxicity of Bt-foods, I was surprised that a large number of studies have been carried out internationally to try and evaluate the possible toxigenic effects of the protein. While respected experts in the fields of agriculture and genetics agree that it is virtually impossible to be able to predict accurately the long-term effects of consuming Genetically modified food-crops, they stress the need for detailed evaluations of toxicity and protein analysis in such plants. An article by Prof. Joe Cummins outlines some important studies on the Bt- Cry Toxin in several animal models and the startling findings reported therein. However, he very pertinently notes that these adverse effects are seldom reported in documents released by Regulatory Authorities in general. He further makes the point that each and every new toxin produced in GM crop needs to be evaluated independently for toxicity in mammals and to the environment. This makes the process long and costly. Citing the case of North America, he says that all the Bt crops approved there were done so simply on the basis of the knowledge on toxicity of the Natural Bt-Toxin and not the synthetically produced toxins. Regulatory authorities simply assumed that if the modified protein bore similar domains and an immunological relationship with the natural toxin, then it was safe. Thus, the actual toxins from any of the modified plants have not been extracted and tested per se.

This is interesting as it seems to underline the general reticence of regulatory authorities to take a strong stand against the hasty introduction of technology being pushed by MNCs for their own vested interests. In the Indian context it is important for authorities to take note of these expert observations.

Dr. Arpad Pusztai

World-renowned expert in the field of lectin study and animal testing of GM foods, Dr. Arpad Pusztai has written a comprehensive article on the subject. He writes that there are no peer-reviewed articles on Human Clinical Trials of Bt or any other modified toxin. Animal study data is equally scarce. The theory of ‘Substantial equivalence’ allows genetically modified crop plants to be patented without any animal trials. This allows for comparison to be drawn between the modified plant and the natural one. If there is found to be no substantial difference between them, then the modified crop is presumed safe and allowed to be commercialized. This is a fundamentally unsound presumption as the modified crop may contain modified proteins that may be allergenic or may cause other problems to humans. The genetic elements used in the modification process may not be completely degraded in the digestive tracts and these reticent genes may be taken up by gut bacteria and result into highly resistant species. Further, inserted genes may express themselves in new and unpredicted ways and may create unknown toxins and allergens which might be difficult to test for, given the absence of anti-sera to these putative toxins/proteins. It is also wrong to assume he says that proteins are allergic only if present in large quantities. Current toxicity testing revolves around testing of micro/macro nutrients in food and evaluation of known toxins only. This system is outdated and newer methods and test need to be devised urgently before allowing these modified crops to enter the food chain. He outlines several of the “studies on GM foods” carried out in the US and points out meticulously the flaws in each of these.³ Some of these I have outlined at the start of the article. All of this data suggests again an almost universal apathy to the possible side-effects of this technology.

In the Indian context again, it interested me to note that Dr. Puzstai, had submitted to the Supreme Court of India an affidavit regarding the GEAC and its haste in allowing Bt-Brinjal commercial trials. In his opening statement without mincing his words he writes, I am afraid, we are still back to the same old problem: the absence of data in the submission for allowing the large scale field trial of Bt brinjal it is impossible to formulate a critical evaluation of the proposal. Unless if now there is access to the GEAC arguments in favour of Bt brinjal large-scale field trials that are based on actual results, hard data and SCIENCE and not PR one can only exchange opinions and insults with the GEAC. Their assurances that they have these results but will not disclose them to us for evaluation are worthless.” In a detailed document he outlines several studies quoting references and papers. I would urge the readers to go through some of these research articles which have not yet received the attention they deserve. ⁴ Among the issues covered by these papers are the fact that the Bt- toxin has now been proved to bind to the gut of mammals leading to a range of problems; The capacity of various A-B toxin-lectins, including Bacillus thuringiensis (Bt) Cry1Ac protoxin to stimulate and modulate both the systemic and mucosal immune systems ; the effects of toxins on the gut linig and liver of various animal models used. Ending this rather shocking affidavit he says and I quote again, “The evidence for the survival of the Bt toxins in the digestive tract and internal organs is clear-cut. Thus, it is expected that the situation with Bt brinjal will not be different. Accordingly, all the already described potentially harmful effects on consumers of the Bt toxins can also be expected to occur with Bt brinjal. As their release into the environment is an irreversible act, sanctioning such large scale field trials would be highly irresponsible.” ⁴

Dr Krishna.R.Dronamraju

Another extremely important opinion has been expressed by the eminent and highly respected Indian scientist Dr Krishna Rao Dronamraju, professor of Genetics in Johns Hopkins and the University of Texas. In an article titled “Bt Brinjal — Why are we rushing into this so fast?”, he calls for a 2 year moratorium on Bt- Brinjal before further consideration. He has clearly stated that India lacks the necessary testing facilities for genetically modified food-crops. He also hints at the possible politicization of the issue pointing out the haste with which the decision to commercialize was taken. But of course what I felt was the difference in his statement was the fact that he questions the premise that this technology will help the farmers in any way. He say and I quote “Even if it were viable, Bt Brinjal is a poor idea,’’ said he. “It is not a staple — why not focus on some crop central to survival, like wheat or rice? We must ask ourselves if it is even necessary.’’ Further, he goes on to say, “And the motives of Monsanto, Bt Brinjal’s producer, were suspect as well. Large corporations are not interested in the public good,’’ he said, adding: “In the case of Monsanto, they knew for years Bt Corn was toxic but tried to cover it up. They released their data only when forced to.’’

I would like to emphasis here one theme that constantly struck me. We are talking about having a scientific debate on an issue that has crucial health and socio-economic implications. Yet, we chose to ignore the very scientific data that should have had centre-stage. The minister claims that all decision will be taken in the light of scientific knowledge and public good. What I have outlined above are just few of the eminent voices talking about the very real dangers of this technology being introduced without extensive and meticulous testing. New technology cannot be evaluated using old standards. And if the evaluation needs to be stalled while these techniques are being developed, then I think it will be worth our while. Also, world-over we need to be able to develop scientific systems that are independent and unafraid of political regimes. All of the scientists I have quoted in this article are people who have dedicated their lives to development of new technologies. However, they are conscientious enough to want to put their research through the acid-test before they can gain any benefits commercial of otherwise though it. I think that is what good science is all about. I think I would not be wrong in saying that the Bt-Brinjal debate has now united the world and I think that is a positive aspect. We have a number of respected individuals in the fields of Science and Environment who have expressed objectively their concerns. While people like me wait with bated breath the decision of the minister on the 10^th of this month, there are a lot of lessons to be learnt from this episode. The most important I think is this; technological advances are necessary and are the only way out of the crisis that looms ahead. But these advances should be sustainable, socially friendly and environmentally sound. Dr. Vandana Shiva has demanded that scientific studies be undertaken to evaluate the real differences between organic farming and Technology driven (GM oriented) farming. I think such studies, if systematically carried out will provide the answers to many nagging problems and will enable farmers and Governments to make really informed decisions.

So, dear readers, ponder over this as we await the decision on the fate of our beloved Brinjal!!!

REFERENCES:

1.The Times of India

2. http://www.indianexpress.com/news/Bt-brinjal-debate–Experts-say-scientific-frauds-being-committed-by-MNCs/576325

3. http://www.actionbioscience.org/biotech/pusztai.html#primer

4. http://www.gmwatch.eu/latest-listing/1-news-items/11868-bt-brinjal-affidavit-by-dr-arpad-pusztai

5. www.foundationforgeneticresearch.com

The New Year has begun and this year, 2010 is to be celebrated as the year of Biodiversity. I am enjoying the delicious irony of this situation, as one of the most hotly debated topics today in India is that of the first- ever genetically modified food to be approved for direct human consumption in the world, namely the Bt-Brinjal. Also known as Aubergine, this humble vegetable is consumed across the length and breadth of India; we are home to about 2500 varieties of this plant.  I can think of no better mascot for Biodiversity than the Brinjal. One of the key aspects that is worrying people in India is the probable loss of indigenously cultivated varieties of this plant because of its GM cousin. The debate over the approval of the Commercialization of Bt-Brinjal by the GEAC in India continues to rage in all circles. Like all great issues, this one has united people in India across all sections of Society.

In October 2009, the GEAC in India cleared the commercialization of the genetically modified Brinjal, the Bt-Brinjal. The vegetable has been modified to contain genes from the Soil Bacterium Bacillus thuringiensis. These genes encode resistance to certain pests of the Lepidoptera family of pests. However, immediately after this decision, there was furious opposition to it by farmers groups, NGOs and Environmental activists such as Dr. Vandana Shiva. The reasons? Well there were many. The failure of a similar non-crop plant, Bt-Cotton to deliver on its promises of pest resistance, the criminal pricing policy of the company involved in the marketing of both the crops in question, namely, the international biotechnology giant Monsanto, the increase in the cases of suicides of small and Marginal farmers in areas where Bt-cotton was being cultivated, to name just a few.

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From the time Gautheret worked with encouraging results in the young field of PTC in 1934 and the problem of tissue culture of plant cells was definitely solved in 1939, independently by Gautheret, Nobécourt and White, the field has come a long way. With more than ten thousand researchers actively engaged in this field of research¹ the technique has undergone massive changes in method and application. From the more academic applications of trying to demonstrate totipotency and wound healing effects to generation of entirely new plants with the view to transplanting them in fields, we have witnessed the growth of an important tool of biotechnology.

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In a significant move, the Ministry of Agriculture in China has granted safety certificates to three genetically modified crop plants;two strains of GM rice and one strain of GM maize. This green signal will enable the commencement of small-scale field trials of these crops in China. This is interesting to those who have been following the intense debate raging over the GEAC’s approval to Bt  Brinjal in India. Though these approvals are only to start field trials and the actual cultivation of GM crops in China is still a far-cry, it will be interesting to see whether this move will have an impact in Asia as a whole with respect to GM technology. The two rice strains have been engineered to carry pest-resistant genes and the maize strain carries a gene that will improve phosphate digestion in animals resulting in better growth and reduction of Phosphate pollution. The former has been developed by Huazhong Agricultural University, and the latter by the Chinese Academy of Agricultural Sciences. The approval had been granted in the month of August but it has become public only lately after recieving local media attention.

The move has drawn criticism from Greenpeace and other environmental groups that are strongly opposed to the use of GM technology. This also happens to be the first time that such a certificate has been granted to a staple food in China. The chair of the International Service for the Acquisition of Agri-biotech Applications, Clive James, wrote in Crop Biotech Update that this is a move that will have a huge impact in Asia. Deeming the move as Global Leadership, he has envisaged an increase in adoption of feed crops as well as food crops in the region as other countries could be expected to follow China. Once again this reminds us that there are relatively few GM crops in the world that are produced for direct human consumption.

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As far as achievements go, this one is huge! Well maybe I am a bit biased towards progress in the life sciences vis-a-vis other fields. Be that as it may, even the severest critics will surely agree that this was probably the most quietly efficient achievements by our researchers. Two thirty-something researchers working with a team of researchers in Institute of Genomics and Integrative Biology (IGIB), Delhi, over a period of close to 2 years, have furnished us with India’s first-ever complete Human Genome Sequence. Using a miniscule 10 ml of blood, scientists mapped out 99% of the genome sequence of a healthy man, 55 years old and a resident of Jharkhand in Northern India. The reason he was chosen for this endeavour, was that though healthy, he was very close to the onset age of certain critical diseases.

The complete sequence is expected to be out in the next two weeks. The two young scientists leading this effort were Dr. S Sridhar and Dr. Vinod Scaria. While the actual sequencing took only an unbelievable 45 days, the setting up of all facilities including software and analysis systems took all of two years. I am all the more elated about this achievement because ironically, India was not a part of the global effort of the HGP (Human Genome Sequencing Project) a few years ago. In an eye-opening article in the Hindu, the ex-director of CCMB, Dr. Pushpa Bhargava, holds the apathy of India’s apex Biotechnology body, the Department of Biotechnology (DBT), solely responsible for what she calls India’s missed opportunity. Citing hard facts and numbers, she builds a case for how India could have played an active role in the sequencing process and today would have been reaping benefits not only in terms of  the prestige in the scientific community, but also in terms of financial gains by patenting STRs (Short Tandem repeats) in the genome. This is exactly what has been done by Celera Genomics, the company that won the sequencing race.

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Try your hand at Puzzle Over This! #4

Some Facts:

• Spurious or fake pharmaceutical drugs (Medicines) are becoming a rising concern in the World.
• WHO (World Health Organisation) defines a spurious drug as “a medicine, which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging.” ¹
• 35% of the world’s spurious medicines come from India ²
• Drugs with insufficient active ingredients such as Antibiotics are leading to the rise of antibiotic resistant strains of microbes, known as superbugs. Some organisms such as MRSA (Methicillin resistant Staphylococcus aureus are today the leading cause of hospital acquired infections.
• A study estimated that in 2005, there were more than 18,000 deaths due to invasive MRSA in the United States ³
• The FDA (Food and Drug Administration) has called for all Pharmaceutical drugs, Biological products like blood ,etc. To be barcoded. ⁴
• Japan calls for similar measures ⁵
• India has no such policy provisions in the near future
• Bar coding and RFID (Radio Frequency Identification) are being considered to prevent counterfeiting in the US and EU.

I was randomly scanning the news one afternoon when I came across some disturbing Statistics. The newspaper claimed that around 35% of the world’s fake pharmaceutical drugs came from India. The European Union, the US and Japan are seriously concerned about the increasing numbers of fake drugs entering organized set-ups such as Hospitals. Now, why should a biotechnologist be concerned about fake drugs? Well, there is a humanitarian concern, of course. Fake drugs are not like pirated movies or books. These drugs can cause serious harm to patients who depend on life-saving drugs for existence; these medicines can kill! Apart from this there is one area that is troubling epidemiologists, drug developers, Medical fraternity and researchers alike. That is, the emergence of Antibiotic resistant strains of deadly bacteria. These organisms, now known as Superbugs, are the cause of some of the most deadly Hospital acquired (Nosocomial) infections. One well-cited example is that of Staphylococcus aureus a gram positive coccus that appears like a bunch of grapes, it is a common cause of Skin ailments, suppurative infections of burns and wounds and Toxic shock syndrome (TSS). There was a time when antibiotics of the penicillin family could be used to cure these infections. However, in recent time, to our growing horror we have seen emergence of a strain of S. aureus that is resistant to the most strong of all drugs and that is methicillin. This organism that is now known as MRSA, (Methicillin Resistant Staphylococcus aureus) is responsible for around 18,000 deaths in the US, (Statistics 2005). There are many such organisms that have emerged in the recent past.

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Some Facts :

• Bt-Brinjals approved for Cultivation in India by GEAC.

• This is the only GM (Genetically Modified) Crop for direct Human Consumption in the World

• No GM food for direct consumption Is available in any supermarket in the EU

• GM soya and GM corn are used as animal feed or in processed form only

• The Cartagena Protocol has provisions that prevent Modification of Indigenous varieties of Crops

• There is really no data available on the effects of the Bt-Toxin on Human beings

• Environmental activists Like Dr. Vandana Shiva and Dr.Sunita Narain strongly oppose the approval.

• Eminent scientist and Chairperson of Moleular Biology at University of Caen in France, Gilles-Eric Seralini, pronounced the data submitted by Monsanto-MAHYCO as insufficient and misleading on several counts and the GEAC wanting in diligence.

• He further hoped we would not turn our people into “lab Rats”

When I read Aldous Huxley’s Brave New World, I was in school. I was fascinated by the world of genetics and genetic engineering and the prospect of solving major problems related to health and food security with a switch of a gene. Well yeah that was my concept of genetic engineering as a clear-eyed 13-year old. Brave New World hooked me because of what I deemed the author’s fertile imagination. Of course we would be manipulating genes, but that would be for curing cancer or Alzheimer’s, not for creating Alpha or beta babies, carefully selected by an authoritarian government in a high tech avatar of caste or race discrimination. What really hit home was this; in the real world, one may belong to a “lower” caste, or an “inferior” race, but what Nature gave you in a universal draw of lots was still yours, nothing or no one could take that away from you. But in the Brave New World, a nameless group of people with ulterior motives, picked and chose genetic traits and created a whole class of people who could or could not do certain levels of work. So, we had the Intellectuals and the Menials with a seemingly irreversible set of traits “given” not by nature but by man. This was what I believed would never really happen. What the hell are laws for? And are people of Democratic States not aware that “Eternal Vigilance is the Price of Democracy”? Then how would such people allow the creation of A Brave New World?  I guess I could be forgiven for such Utopian fantasies, I was just a kid.

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The detection and cure of cancer has become increasingly essential as a large number of people continue to succumb annually to this deadly disease. Treatment in the case of cancers poses a unique problem in terms of the high potential toxicity of many of the drugs currently being used in cancer therapy. Additionally, the fact that any method of killing cancerous cells also inevitably causes harm to normal, healthy cells and tissues further complicates the situation. Thus researchers have to find answers to some very crucial questions: First, can they reduce the effective dosage of the drug in question in order to reduce the magnitude of the damage to unwanted tissues? And second, can they control the release of the drug and or localize the drug to a specific set of cells within a tumour or in areas near it, thus preventing tissue damage? These are tough problems to tackle, especially when working with a complex system such as the human body. There is a limit to which one can reduce dosage, since one has to allow for loss of the drug through physiological processes within the body. Too low a dose might end up not really being efficacious. Localization however will end up solving both problems. If the drug can be localised, even relatively smaller doses can prove to be more efficient.

It was when I pondering over these problems that I came across some research carried out in the field of nanotechnology that was concerned with precisely the same problems. Researchers have come very close to solving the problem of localized and metered dosing of a drug within the body. This feat has been achieved by using gold nanocages. These cages are coated with a special type of “smart polymer” which can be induced to open or close using an external signal such as exposure to near-infrared light. These smart polymers are very apt for use in timed release of drugs.

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I recently read a press- release that very attractively used the term fly-paper to describe a novel invention by researchers at UCLA that can be used to grab maverick cancer cells circulating in the blood stream. These ‘mavericks’ I might add are known in Cancer jargon as Circulating Tumour Cells or CTCs. These tumour cells escape from an already formed tumour in the body and begin to circulate in the body via the bloodstream that involuntarily acts as a transport medium for these dangerous cells. The CTCs now form newer tumours in locations distinct from that of the original tumour, resulting in formation of ‘satellite tumours’ or colonies of tumour cells, giving rise to one of the most Distinctive and scaring features of a malignant tumour, namely, Metastasis.

A Cirulating Tumor Cell

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