Thursday, 30 October 2008

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.

Monday, 27 October 2008

Biofriendly’s UK sister company Green Plus releases details of E.ON report

The recent report by E.ON Power Technology in the United Kingdom shows us details of testing done on Green plus, liquid fuel catalyst that reduces harmful emissions, in a test boiler of a coal-fired power plant. Green Plus is a sister company to the Biofriendly Corporation in the US. The purpose of the test was to determine how the fuel catalyst's ability to improve combustion would affect the efficiency of the power plant. The report shows promising results when Green Plus is added to a coal-fired generator.

The report states, "The Green Plus Catalyst showed benefits in LOI (Loss on Ignition) carbon burnout, with no increase in NOx (Nitrogen Oxides) and in some cases, a small NOx reduction." LOI defines the amount of unburned carbon in fly ash. A lower LOI represents less carbon residue in the ash, which means the boiler is operating more efficiently, with lower emissions. During the test, Green Plus lowered LOI by at least 20%.

Alan Thompson, a member of the Test & Measurement Group from Power Technology stated, "This was a very interesting test where the Green Plus catalyst for pulverized coal firing showed benefits in LOI reduction with no increase in NOx." The fact that the research boiler at Power Technology is optimized for low LOI and low NOx makes the test result even more remarkable.

"Reducing the percentage of unburned carbon (LOI) without increasing airflow and keeping NOx emissions under control or even lower than before could be extremely useful to the power industry," said Dr. Colin K. Hill, Chief Consulting Scientist for Biofriendly Corporation. "It may give the industry new flexibility in fueling and power output options. We plan to confirm these research boiler test results on a full scale commercial power plant shortly," he added.

Decreasing unburned carbon may also increase the efficiency of the boiler without increasing the production of NOx in coal-fired power plants. This opens up an entire new market to Biofriendly Corporation and Green Plus Ltd, and it shows that Green Plus has additional potential applications when it comes to improving combustion. Furthermore, this test result is another in a long line of positive independent and certified tests of Green Plus. Each of these third party results supports the claim that Green Plus is the world's most effective and economical solution for significantly reducing emissions, improving fuel economy and enhancing engine performance.

Sunday, 26 October 2008

Green Plus is now mandated in Mexican City of Guzman to help clean air

Biofriendly Corporation has mandated that the Mexican City of Guzman (population 120,000) use fuel (gasoline and diesel) treated with Green plus liquid fuel combustion catalyst. All city vehicles, private buses and taxis are to use Green Plus, which is designed to reduce harmful emissions and improve performance. Guzman is the first city in Mexico to implement the "Emission Zero" program recently passed by the State of Jalisco.

The President (Mayor) of the City of Guzman spoke of the new environmentally friendly advancement, with the full support of the City Council (100% vote) and from other Mexican states and members of the Jalisco Congress and American Consul. Representatives of major corporations including Coca-Cola, Bimbo, Comision Federal de Electricidad y Telefonos de Mexico as well as the Regional Director for Pemex, and the national oil company also took part in the release of their new advancement towards a cleaner and safer environment.

Congressman (Diputado) Luis Alejandro Rodriguez, President of the State of Jalisco Congressional Environmental Commission said, "The City of Guzman inaugurates the start of our state program "EMISION ZERO" to clean up the air in Jalisco. We intend to be proactive about cleaning up our environment and we expect this to become a model for all of Mexico."

The Mayor of Guzman, Umberto Alvarez Gonzales said, "We have to stop robbing the clean air from our children and citizens, we are all breathing the same dirty air. "EMISION ZERO" gives us a chance to reverse this trend."

Prior to the implementation of this program a certified test was completed. Angel Ricardo Martinez, Director of Vehicle Environment Enforcement (Semades) for the state of Jalisco monitored and certified the pilot program that showed diesel opacity reductions of over 56%.

Correct Action International; the distributor of Green Plus in Latin America has been invited to meet with another state congress and other cities that want to adopt the "EMISION ZERO" program.

The state of Jalisco includes famous cities like Guadalajara, Puerto Vallarta, Tequila, and now the City of Guzman, the first city to take action in support of "EMISION ZERO' using Biofriendly's Green Plus to clean up the air.

Saturday, 25 October 2008

Indian Biotech Market - Firm And Steady Growth

Biotechnology sector of India is not a new one. It has been nourished since its inception by national government. Nevertheless, this industry is still in the infant stage. Currently, India is investing in academics and existing industry's infrastructure considerably to expedite the overall growth of sector.

Biopharma sector enjoys the major share of the total biotech market. It comprises of therapeutics, vaccines, animal health care products and diagnostics. Notably, whenever any Indian biopharma company releases its products in market, MNCs reduce prices for these products to vie. The bioindustrial segment consists of organic amino acids, enzymes, yeast and yeast-based products and account for over 10% of the total market share. These products, actually, were first off the mark from the biotech industry of India.

In India most of the bio drugs and diagnostic products are for the government and private sector hospitals and patients. The second group of buyers of biotechnology products and biomolecules are the research institutes and pharmaceutical companies. The emerging trend of corporate players establishing diagnostic centers in small towns and rural areas is providing opportunities for the import of automated systems and imported reagents.

Patients and private and government hospitals are the main consumers of diagnostic products and bio drugs in India. Pharmaceutical companies and research institutes are the second set of consumers of biomolecules and biotechnology products. The evolving trend of establishing diagnostic centers in rural areas and small towns by corporate houses is giving the opportunities for the import of reagents and automated systems.

Indian biotech market is very promising. Though there is a great scope for investments and import in healthcare biotechnology sector of India still the industry is facing many challenges; first being inadequate IP (intellectual property) protection. India pledged to product patent by improving its patent law in 2005. Therefore, firstly, some entrepreneurs lead the industry and dispersed research supported by government. IP should be protected through proper implication is necessary for the development of product. Second challenge is that majority of the healthcare expense is "out of pocket expenditure". As a result, the new innovative drugs, which are costly and can't be afforded by Indian patients, are not sold in India. It has kept big honchos of global biotechnology sector away from Indian market. But, the increasing coverage in health insurance is changing the market.

Third challenge the industry facing is the shortage of biotechnology experts. Till recently, government institutes, in cooperation with private ones, conducted most of the biotech research. Now many education institutes, like schools and colleges, have introduced the courses in biotech.

Indian Biotech Industry Successful IT cousin

Closely following information technology, the next success in India is biotechnology. As per Mckinsey by 2020, only two main biotechnology companies will comprise a market capitalization, which will be the same as the collective market capitalization of all of the IT companies at present.

This rapid growth in biotechnology is working as an incentive to bio-industry executives, research scientists, and venture capitalists to come together to put forth ideas that would triple the market for bio-products. The latest inclination is towards the application of IT to biotechnology, transgenic crops, plant genomes, crop protection, food security, and induced resistance to plant diseases. With this in the background a number of biotechnology researchers want to become entrepreneurs.

The world currently spends about US $7 billion on outsourced biotech R&D. Further this is expected to grow by 30% every year for the next 5 years. Also there is a growing increase in the global trend to outsource R&D to areas of lower-cost capabilities in biotechnology. CROs can be compared with software development in the IT sector in terms of the formers activity and they have a potential to function as export oriented units.

Bio-informatics can prosper relatively easily through the development of software to handle biological data. Biotechnology is the most updated division of science, which is believed to have immense potential in agriculture and environment.

In their market research report, “Indian Biotechnology Market Outlook (2006)” RNCOS’ analysts reveal that the present biotech workforce employed in India is 10,000 and this is expected to double in 2006. Of this total workforce 50% will be in research, 35%in the technical and services sector, and 15% in management.

The report gives a clear picture of the future Indian biotech market, the initiatives and policies of central and state governments covering all segments of the market. Having made an intensive SWOT analysis the report analyzes the sector in terms of size, demand, and foreign and domestic markets for 2005 while making forecasts till 2010.

Finally the report lists company profiles of 20 major companies in the biotech industry including Shantha Biotechnics, Biocon, Bharat Biotech, Wockhardt, Serum Institute of India, Zydus Cadila, and Aventis Pharma.

Friday, 24 October 2008

CRM System

f you want to choose the CRM system that suits your business there are many CRM solution companies that can try to woo you. You have many alternatives. Choosing one of them could be a daunting task because you want to be sure that by availing these services you are not going to lose any customer or client. Sometimes the buyer of the CRM Systems repents for not taking the help of call centre outsourcing.
1. Clarify whether CRM system is on site or web based.
2. The new form of effective CRM solution is the web based CRM. This web based CRM is also called hosted CRM. This is taking the place of onsite CRM systems. The advantages of the web based CRM system are adaptability, flexibility and continuous connectivity. These three features are very important for the success of the CRM system
3. On the contrary the onsite CRM system is more in details. For onsite CRM system the employees may be required to undergo additional training. The infrastructure needed for onsite CRM system and related CRM implementation is costly.
4. Ask for a no obligation trial time.
5. Get the CRM system on trial basis at least for a month and once satisfied with the performance then only pay.
6. Check the Security checks offered in the CRM system. Sometime some information needs to be classified and not meant for everyone.
7. See to it that the CRM system gets fully integrated into your organization. Special care has to be taken for integration at the level of business process and business objects.

8. Do not get attracted by the brand name ,image or name of the CRM Consultancy. At the end of the day the system should be beneficial for your business and not a non performing asset.
9. Most of the people buy a CRM system because their friends bought and when it does not perform then they repent about it. Do not buy any CRM system that does not serve your purpose. Do not go by what others say because it is not going to be their investment, it is going to be your hard earned money.
10. Do not get lured by the discount offered. Sometimes the discount is offered just to get rid of that product.
11. Never pay lump sum charges for the CRM system.
12. It may not be wise enough to buy a generalized box packed CRM solution.
13. Never sign the service level agreement without reading and understand the details mentioned therein especially those related to downtime clauses during maintenance.

Friday, 3 October 2008


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


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.


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.

Thursday, 2 October 2008

Blend It Yourself

OK, so I picked up a free copy of the Industrial Biotechnology journal at this weeks SIM meeting and in it they had something that caught my eye. It is a small company called E-Fuel that is coming out with a home ethanol distilling system. Yes, you read that right. It is a big box with a gas pump on it that you dump raw sugar and yeast into and out comes ethanol. Apparently it uses membrane distilling instead of traditional heat distilling so things won’t explode on you. They claim that making a gallon of ethanol costs about $1.25 and that you can even dump alcoholic drinks into it and run them straight through the membrane system to recover the ethanol in there for $0.10 a gallon.

The E-Fuel home ethanol production system

The E-Fuel home ethanol production system

I’m not too sure who is going to buy this thing. I can’t imagine your average joe going out and buying big sacks of sugar (it takes about 10lbs per gallon) to feed this thing. Especially if you live in a humid climate, your sugar will be slowly decompose on you sitting in your garage (not to mention your massive new ant problem). I suppose that it does make sense for some customers. If you are a winery or brewery that does have large amounts of alcohol that you discard this could make sense (not to mention your local colleges fraternity - all that stale beer will be put to good use on Sunday mornings). I can also imagine a big aftermarket and hack culture growing up around this thing. People will make mods to use starches and maybe even cellulose efficiently and since it’s basically a rum refinery in your driveway, I can imagine mods to create your drink of choice. Maybe modify the membrane to be not so perfect in its operation and let some of the impurities through that would make a good hard liquor.

Wednesday, 1 October 2008

The history of gene therapy

In the early 1970s, scientists proposed "gene surgery" for treating inherited diseases caused by faulty genes. The idea was to take out the disease-causing gene and surgically implant a gene that functioned properly. Although sound in theory, scientists, then and now, lack the biological knowledge or technical expertise needed to perform such a precise surgery in the human body.

However, in 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific type of protein) for correcting the disease was injected into a group of cells for replication. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease, thus correcting the genetic defect that caused the disease.

As the science of genetics advanced throughout the 1980s, gene therapy gained an established foothold in the minds of medical scientists as a promising approach to treatments for specific diseases. One of the major reasons for the growth of gene therapy was scientists' increasing ability to identify the specific genetic malfunctions that caused inherited diseases. Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific genetic abnormalities in one or more genes occurred in successive generations of certain family members who suffered from diseases like intestinal cancer, bipolar disorder, Alzheimer's disease, heart disease, diabetes, and many more. Although the genes may not be the only cause of the disease in all cases, they may make certain individuals more susceptible to developing the disease because of environmental influences, like smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic component.

On September 14, 1990, a four-year old girl suffering from a genetic disorder that prevented her body from producing a crucial enzyme became the first person to undergo gene therapy in the United States. Because her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening infections. W. French Anderson and colleagues at the National Institutes of Health's Clinical Center in Bethesda, Maryland, took white blood cells (which are crucial to proper immune system functioning) from the girl, inserted ADA producing genes into them, and then transfused the cells back into the patient. Although the young girl continued to show an increased ability to produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.

Nevertheless, a new era of gene therapy began as more and more scientists sought to conduct clinical trial (testing in humans) research in this area. In that same year, gene therapy was tested on patients suffering from melanoma (skin cancer). The goal was to help them produce antibodies (disease fighting substances in the immune system) to battle the cancer.

These experiments have spawned an ever growing number of attempts at gene therapies designed to perform a variety of functions in the body. For example, a gene therapy for cystic fibrosis aims to supply a gene that alters cells, enabling them to produce a specific protein to battle the disease. Another approach was used for brain cancer patients, in which the inserted gene was designed to make the cancer cells more likely to respond to drug treatment. Another gene therapy approach for patients suffering from artery blockage, which can lead to strokes, induces the growth of new blood vessels near clogged arteries, thus ensuring normal blood circulation.

Currently, there are a host of new gene therapy agents in clinical trials. In the United States, both nucleic acid based (in vivo) treatments and cell-based (ex vivo) treatments are being investigated. Nucleic acid based gene therapy uses vectors (like viruses) to deliver modified genes to target cells. Cell-based gene therapy techniques remove cells from the patient in order to genetically alter them then reintroduce them to the patient's body. Presently, gene therapies for the following diseases are being developed: cystic fibrosis (using adenoviral vector), HIV infection (cell-based), malignant melanoma (cell-based), Duchenne muscular dystrophy (cell-based), hemophilia B (cell-based), kidney cancer (cell-based), Gaucher's Disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector). When a cell or individual is treated using gene therapy and successful incorporation of engineered genes has occurred, the cell or individual is said to be transgenic.

The medical establishment's contribution to transgenic research has been supported by increased government funding. In 1991, the U.S. government provided $58 million for gene therapy research, with increases in funding of $15-40 million dollars a year over the following four years. With fierce competition over the promise of societal benefit in addition to huge profits, large pharmaceutical corporations have moved to the forefront of transgenic research. In an effort to be first in developing new therapies, and armed with billions of dollars of research funds, such corporations are making impressive strides toward making gene therapy a viable reality in the treatment of once elusive diseases.

Gene Therapy - Viral Vectors

In both types of therapy, scientists need something to transport either the entire gene or a recombinant DNA to the cell's nucleus, where the chromosomes and DNA reside. In essence, vectors are molecular delivery trucks. One of the first and most popular vectors developed were viruses because they invade cells as part of the natural infection process. Viruses have the potential to be excellent vectors because they have a specific relationship with the host in that they colonize certain cell types and tissues in specific organs. As a result, vectors are chosen according to their attraction to certain cells and areas of the body.

One of the first vectors used was retroviruses. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biological action. They also have learned how to remove the genetic information that governs viral replication, thus reducing the chances of infection.

Retroviruses work best in actively dividing cells, but cells in the body are relatively stable and do not divide often. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from the patient's body, and the virus, or vector, carrying the gene is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they will provide the desired therapy.

Another class of viruses, called the adenoviruses, also may prove to be good gene vectors. These viruses can effectively infect nondividing cells in the body, where the desired gene product then is expressed naturally. In addition to being a more efficient approach to gene transportation, these viruses, which cause respiratory infections, are more easily purified and made stable than retroviruses, resulting in less chance of an unwanted viral infection. However, these viruses live for several days in the body, and some concern surrounds the possibility of infecting others with the viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a herpes virus that infects nerve cells.

Scientists also have delved into nonviral vectors. These vectors rely on the natural biological process in which cells uptake (or gather) macromolecules. One approach is to use liposomes, globules of fat produced by the body and taken up by cells. Scientists also are investigating the introduction of raw recombinant DNA by injecting it into the bloodstream or placing it on microscopic beads of gold shot into the skin with a "gene-gun." Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that have a high molecular weight and formed by smaller molecules of the same or similar substances), is "constructed" in the laboratory by combining these smaller molecules. They have been used in manufacturing Styrofoam, polyethylene cartons, and Plexiglass. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They also can be designed to form an affinity for particular cell membranes by attaching to certain sugars and protein groups.