Tuesday, July 10, 2012

Creative Explosion: European caves or South African Caves?

Creative Explosion: European caves or South African Caves?

TOOLS and BEYOND. Back again and trying to catch up with some news. An article published in the August issue of Scientific American magazine presents a general review from the work conducted in the last two decades by archaeologist Curtis Marean and his team on coastal South African sites. His main findings challenge the previous hypothesis that suggests that earliest modern human behaviors were all found in Europe around 40,000 years ago (and suggesting that this was the departure "place"). The authors wrote that at Pinnacle Point they found evidence that supports the idea that modern humans (at Pinnacle Point) "may be very well the ancestors of everyone in the planet". Marean an colleagues published similar findings in other South African sites such as Blombos Cave suggesting that modern human behaviors emerged earlier that previously accepted. Maybe we must recognize that the "creative explosion" leading to modern human behavior happened at different times in different regions....(by the way, what's the meaning of "modern human behavior?)
If you want to learn more about Pinnacle Point, and the findings presented by Marean and colleagues, you can check a very entertaining link created by Scientific American.

The biological basis of gene therapy

The biological basis of gene therapy
Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not, in essence, doing their job. Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic defects that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases, like cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancers, arthritis, and infectious diseases. Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, like intelligence or appearance.

The biological basis of gene therapy

Gene therapy has grown out of the science of genetics or how heredity works. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within the cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of a single molecule of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that determine inherited characteristics.

A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each other. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen molecules and arranged in specific sequences. Millions of these base pairs, or sequences, can make up a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs ultimately direct an organism's growth and characteristics through the production of certain chemicals, primarily proteins, which carry out most of the body's chemical functions and biological reactions.

Scientists have long known that alterations in genes present within cells can cause inherited diseases like cystic fibrosis, sickle-cell anemia, and hemophilia. Similarly, errors in the total number of chromosomes can cause conditions such as Down syndrome or Turner's syndrome. As the study of genetics advanced, however, scientists learned that an altered genetic sequence also can make people more susceptible to diseases, like atherosclerosis, cancer, and even schizophrenia. These diseases have a genetic component, but also are influenced by environmental factors (like diet and lifestyle). The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process by either replacing missing genes or providing copies of functioning genes to replace nonfunctioning ones. The inserted genes can be naturally-occurring genes that produce the desired effect or may be genetically engineered (or altered) genes.

Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing the specific genetic sequence desired, then inserting it into the DNA of another gene. The resultant product is called recombinant DNA and the process is genetic engineering.

There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or someday possibly into embryos in hopes of correcting genetic abnormalities that could be passed on to future generations. Most of the current work in applying gene therapy, however, has been in the realm of somatic gene therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual patient.

BIOTECHNOLOGY AND ENVIRONMENTAL BIOSAFETY

BIOTECHNOLOGY AND ENVIRONMENTAL BIOSAFETY

Genetical modification of Agricultural Seeds- cotton, soya, maize, potato, rice and trees in the forest.

Prologue

The all encompassing big macabre issue discussed world wide today is the invasion of the good science, ‘biotechnology’ to virtually every nook and corner of the biosphere and practically turned to the bad science, ‘thanotechnology’ for every living element of concern and speeding up the rate to total annihilation of the biosphere.It all began with a little known episode in 1980, that is the US Supreme Court decision in the case, Diamond vrs. Chakrabarty, where the highest US court decided that biological life was legally patentable.

History

Anand Mohan Chakrabraty a microbiologist and employee of General Electric Company (GE) developed a type of bacteria that could ingest oil from oil spills. GE rushed for a patent in 1971 which was turned down as life forms were not patentable. GE sued and won. In 1985 the US Patent and Trademark Office (PTO) ruled that the Chakrabraty ruling could be further extended to all plants, seeds and plant tissues or to the entire plant kingdom.

US company W.R. Grace was granted 50 US patents on the Indian Neem tree which even included patenting indigenous knowledge of medicinal use of the Neem products (since been leveled ‘biopiracy’). In 1988 PTO issued patent on animal to Harvard Professors, Philip Lader and Timothy A. Stewart who had created a transgenic mouse having genes of the chicken and human being. In 1991, PTO granted patent to human stem cells and later to human genes. Biocyte was awarded European patent on all umbilical cord cells from foetuses and new born babies even without the permission of the ‘donors’. European Patents Office (EPO) received applications from Baylor University for the patenting of women who had been genetically altered to produce GE proteins in their mammary glands.

Baylor University essentially sought monopoly rights over the use of human mammary glands to manufacture pharmaceuticals. Attempts also were made to patent blood cells of indigenous people of Panama, the Solomon Islands and Papua New Guinea. Within a decade the ‘Chakrabarty ruling’ of the US Supreme Court revolutionised the research and developments in biotechnology involving microbes to human beings which led it to be branded as bad science, “thanotechnology” in the following decade and hated world wide. biotech companies engaged in biotech pharmaceuticals quickly moved to agriculture, obtained patents on seeds, buying up small seed companies, destroying their seed stocks and replacing the same with GE seeds. In the last decade several companies have gained monopoly control over such seeds world wide as soy, corn and cotton ( used in processed foods via cotton seed oil). As a result, nearly 2/3 rd. of such processed foods showed some GM ingredient in them.

However, even without any labelings, the concerned US consumers were aware of such pervasive food products of biotech companies. Immediately the companies knew that aware citizen kept away from GM foods and they organized to convince the regulators not to require such labelings. Somewhat shockingly the bureaucratic risk evaluators in the US turned a blind eye towards the ill motives of the bio-tech companies.

The point of concern

All genetical modifications are based on recombinant DNA technology. The present society is faced with unprecedented problems not only in the history of science, but of all life on earth. The GE technology enables the profit oriented biotech companies the capacity to redesign the living organisms, the products of three billion years of evolution. In the words of Dr. George Wald, Nobel Laureate in Medicine (1967), Higgins Professor of Biology at the Harvard University, “potentially it could breed new animal and plant diseases, new sources of cancer and novel epidemics”.

On Record

In 1989, dozens of Americans died and over several thousands were afflicted and impaired owing to the ingestion of a genetically altered version of food supplement L – tryptophan. A settlement of $ 2 billion was paid by Showa Denko, Japan’s 3rd. largest chemical company (Mayeno and Gleich, 1994)

In 1996, pioneer Hi-Bred spliced Brazil nut genes into soy beans. Some individuals are so allergic to this nut that they go into apoplectic shock which can cause death. Animal tests confirmed the peril and the product was soon removed from the market before any fatalities occurred. In the words of Marion Nestle, HOD Nutrition, New York University, “the next case could be less than ideal and public less fortunate.”

In 1994 US Food and Drug Administration approved Monsanto's r-BGH, a GE growth hormone, for injecting the dairy cows to enhance their milk yield in spite of experts warning that the resultant increase of IGF-1, a potent chemical hormone, linked to 400 – 500 % higher risks of human breast, prostrate and colon cancer. According to Dr. Samuel Epstein of University of Chicago, “ it induces the malignant transformation of human breast epithelial cells.” Studies on Rats confirmed the suspicion and showed damage to internal organs with r-BGH ingestion. Even FDA’s own tests showed a spleen mass increase by 46%, a state that is a prelude to ‘leukemia’. The argument that the substance get damaged by pasteurization was nullified by 2 of Monsanto’s own scientists, Ted Elasser and Brian Mc Bride who found only 19% of the hormone get destroyed after 30 minutes of boiling (pasteurization takes only 30 seconds). Inspite of Canada, EU, Australia, New Zealand and even the UN’s Codex Alimentarius refusing to endorse the GE hormone, the same is freely marketed in the US by Monsanto. It was found out that 2 US bureaucrats namely, Margaret Miller and Micheal Taylor in the US FDA who helped Monsanto’s r-BGH pass the risk factor barrier were in fact earlier Monsanto employees.

Several other GM products approved by US FDA involve herbicides that are commonly known as ‘carcinogenic’, viz – ‘bromoxiny’l used on Bt. Cotton and Monsanto's ‘round-up’ or Glufosinate used on GM soy, corn and canola. Sharyn Martin, a researcher, has opined that a number of auto- immune diseases are enhanced by foreign DNA fragments which come with G M food that are not fully digested in the human stomach and intestine. These DNA fragments absorbed into the blood stream mix with normal DNA through recombination and are, hence, unpredictable. Such DNA fragments have been found to be in GM soy and other GM products available in the market.

The fear factor

Professor Joe Cummins, Professor Emeritus of Genetics, University of Western Ontario said, ‘ Virus resistant crops are becoming the mainstay of biotech industries. These crops carry foreign virus genes which are genetically engineered to empower the plants to resist virus attacks. Most of the fruits, vegetables and baby food marketed in the US are of this category. Lab. experiments have shown that ‘the GE viral genes in food potentially give rise to new viruses – deadlier than the viruses that the crops are being protected from’, a fact that is quite alarming.
In 1986, it was reported that GE plants having TMV genes delayed the development of the disease and this report opened the flood gates to create resistance to a range of other viruses. But the fact is that viral coat protein production in GE crop does not block the virus entering into the plant cell rather the transgene is exposed to the nucleic acids of many viruses that are brought to the plant by insect vectors. A number of study results are there to show that plant viruses can acquire a variety of viral genes from GE plants through recombination.

For examples-
* Defective Red Color Mosaic Virus lacks the gene enabling it to move from cell to cell and hence is not infectious ,but recombined with a copy of that gene in GE Nicotina benthamiana plants, regenerated the infectious RCMVirus.
* GE Brassica napus and Nicotiana bigelovii containing “ gene- vi ”, a
translational activator from the Cauliflower Mosaic Virus (CaMV) which
recombined with the complementary part of a virus missing that gene, and
produced new infectious virus in all GE plants.
* N. benthamiana expressing a segment of the Cowpea Chlorotic Mottle Virus (CCMV) coat protein gene recombined more frequently with the defective virus missing that gene.
* N. benthamiana was transformed with 3 different constructs containing coat protein coding sequence of African Cassava Mosaic Virus (ACMV). The transformed plants were inoculated with a coat protein deletion mutant of ACMV that induces mild systemic symptoms in control plants. Several such inoculated plants of the transgenic lines developed severe systemic symptoms typical of ACMV confirming recombination had occurred between mutant viral DNA and the integrated construct DNA resulting in the production of recombined viral progeny with ‘ wild type ’ virulency.

The CaMV recombination, when and where ?

CaMV 35 s promoter gene, is the ubiquitous viral sequence in all the transgenic (GM) plants which are either already commercially released in the market or undergoing field trials. This gene is needed by all GM plant producers because it drives the production of gene messages from the genes inserted to provide herbicide tolerance, insect- pest resistance, antibiotic resistance and a range of other functions deemed to improve the commercial quality of the crop plant. In the absence of this ‘promoter gene’, the ‘inserted gene’ remains inactive, while in its presence the gene activity is maintained at a high level in all of the plant tissues irrespective of the changing environmental conditions which drastically affect the activity of ‘promoters’ native to the crop plant.

The 2 events which occurred in 1999 provoked Professor Cummins and other independent scientists to draw global attention to such alarming industrial scientific maladies that may have disastrous consequences. In fact Professor Cummins had in 1994 questioned the environmental safety of the release of CaMV 35 s promoter gene through the GM plants. Experimental evidences available indicated that the frequency of genetic recombination of CaMV 35 s promoter gene was much higher than those of other viruses. When recombinant CCMV was recovered from 3% of transgenic N. benthamiana containing CCMV sequences, recombinant CaMV was recovered from 36% of transgenic N. begelovii.

Event -1. Scientists of John Innes Research Institute published a paper showing that the CaMV 35 s promoter has a recombination ‘hot spot’ meaning it is prone to break and reassociate with other pieces of genetic material, may be of other viruses.

Event- 2. Dr. Arpad Pusztai, a senior scientist working in the UK govt. funded Rowett Institute in Scotland was sacked from his job because he revealed the results of feeding experiments suggesting that transgenic potatoes were unsafe. The lab. Rats fed with GM food showed increased lymphocytes in gut lining indicating damage to intestine from non specific viral infection.

Scientists Mae- Wan Ho and Angel Ryan published a paper in October 1999 issue of Journal of Microbial Ecology in Health and Disease warning that the CaMV 35 s promoter is interchangeable with promoters of other plant and animal virus and is promiscuous and functions efficiently in all plants, green algae, yeast and E. coli. Its recombination hot spot is flanked by multiple motifs and is similar to other recombination hot spots such as that of the Agrobacterium –T DNA vector, the other most commonly used gene, in making transgenic plants. They also claimed to have demonstrated in the lab. of the recombination between viral transgenes and infecting viruses.

In an article published in the online journal of European Food Research and Technology (2006) authors ( Marit R. Myhre, et. al. ) claimed to have constructed expression vectors with CaMV 35 s promoter inserted in front of 2 ‘reporter genes’ encoding firefly luciferase and green fluorescent protein (GFP), respectively and performed transient transfection experiments in the human enterocyte – like cell line, Caco - 2 and found that the CaMV 35 s promoter genes drive the expressions of both the ‘reporter genes’ to significant levels.

Friday, July 6, 2012

A Major development into the cause of Brain Cancer in children

A Major development into the cause of Brain Cancer in children


A recent breakthrough from a study on paediatric brain cancer, may be the key to finding a cure, or at least much more effective treatment. The study, spearheaded by the Research Institute of the McGill University Health revealed a significant genetic difference between this type of cancer and the adult equivalent (Jeremy Schwartzentruber, 2012). Brain cancer is one of the deadliest of cancers in children, and the most common form of brain cancer, GBM multiforme has an average survival of only 12-17 months even with aggressive treatment. 

 As you may already know, cancer is a disease, which stems from damaged DNA, leading to uncontrolled cell division, and then tumours. Tumours, however, are not always cancerous, and are only malignant if they “invade nearby tissues and spread to other parts of the body” and may return even after being removed through surgical methods. (National Institutes of Health, 2012). Brain cancer is particularly life threatening as it is located in an essential organ of the body, which has limited space. The tumour in the brain may increase the intracranial pressure, which leads to headaches, vomiting, comas, and in children; large bulges in the fontanelles (soft spots which allow the skull flexibility to fit through the birth canal). Other symptoms of brain tumours include many neural dysfunctions ranging from impaired senses to changes in personality to epileptic seizures, which sadly can be explained by many other diseases, and brain cancer can be overlooked. (Charles Patrick Davis, 2012)

 This study sequenced the exomes of 48 children who had GBM and found two genetic mutations which accounted for up to 40% of the GBM in the sample (Science Daily, 2012). An exome is a specific area of the entire genome which are important the creation of particular types of proteins. This method is more efficient, as there are over 180,000 exons in the entire genome, and the “relevant” exons can be sequenced much faster and can detect variations or mutations much more successfully (Sarah B. Ng, 2009).


 Figure 1 MRI of a Glioblastoma multiforme (Eric M. Thompson, 2011)
 The two genetic mutations were:
1.     “Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway in 44% of the tumours” (Jeremy Schwartzentruber, 2012)
2.     “Recurrent mutations in H3F3A, which lead to amino acid substitutions in critical parts of the histone tail in 31% of tumours” (Jeremy Schwartzentruber, 2012)

 According to Dr Jabado of the MUHC, it was not known why children and adolescent GBM patients did not respond to treatments as well as adult patients. The commonplace treatments of chemotherapy and radiotherapy had inexplicably been resisted by tumours in children, which were revealed by this study to be caused by the mutations preventing the treatments to properly target and differentiate cancerous cells from healthy cells. He continued to say that this results “(are) significant here … (as) the first time in humans we have identified a mutation in one of the most important genes that regulates and protects our genetic information. This is the irrefutable proof that our genome, if modified, can lead to cancer and probably other diseases.” (Science Daily, 2012)

This genetic mutation has been detected in other forms of cancer, and the researchers from MUHC are hopeful that this breakthrough will lead to new treatments for cancer in specific patients with these mutations (Hazell, 2012). Continued developments such as these will lead to the future of patient care, which will utilise personalised genome mapping and treatment plans based on the individual.

Genetics in Cancer

Genetics in Cancer

Hello, everyone. Today, I shall discuss the topic of cancer or, more accurately, a recent advance in genetics that should assist us greatly in the fight against cancer. Cancer currently afflicts 112,300 Australians, and causes 39,000 deaths every year (Australian Institute of Health and Welfare 2008). You can see that this is quite an intolerably large figure. Luckily, scientists are becoming able to identify the specific genetic mutations that lead to individual malignant neoplasms (that’s just the smart-people name for cancerous tumours). This innovation lets us give more effective treatment, and undergo greater in-depth analysis of the origins of a cancer.


The University of Colorado

This technique is still in the early stages of development, so scientists are not even close to identifying all of the genetic mutations that cause all types of cancer. However, researchers at the University of Colorado Cancer Centre performed a clinical trial in 2010 in which they did actually manage to link genetic anomalies to cancer. In this case, they studied a particular rearrangement of genes inside the cancer cells of thirteen different lung cancer patients. The study involved testing a drug designed to target this ‘gene rearrangement’ (Camidge 2010).



Diagram of human lungs containing a tumour

These researches managed to show that the identification of genetic mutations in cancer cells allows cancer to be treated very effectively. To see just how effective it is, you can look at the results of the trial for one of its patients, 60-year-old Ellen Pulhamus. Before the study, she had five malignant tumours, which shrunk by 62 percent after just six weeks! In addition to that, another round of treatment brought down their size by a further 50 percent! (Brown 2010) Results as fantastic as these mean that oncologists should soon be able to move on from prescribing drugs that will only work for about one in ten cancer patients, and charge forward to the stage where they can determine exactly which patients will benefit from which treatments, by looking at the genes of their tumours (Brown 2010).


Tumours in a lung


Another goal of the researchers in this field is to try to use gene identification to trace cancer cell mutation back to its origins. This could allow the primary prevention of some cancers by exposing the kinds of lifestyles and environmental conditions that lead to them (Brown 2010). It may even provide current cancer patients with some peace of mind, in that they could find out the reason or reasons behind them being so sick.




Cancer is a tragedy that most of us will have to experience at some point in our lives, whether it be through having to endure it ourselves or witness it in someone close to us. The work done by researchers like those at the University of Colorado Cancer Centre will allow us to extend, or even save, a considerable number of lives, from within our species and perhaps outside it. With cancer being the prevalent calamity that it is, such an achievement will have far-reaching positive consequences for our entire race.