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Genetic scientists have been busy creating all kinds of solutions to some of the problems that the human and agricultural populations have been experiencing. One of the most promising has been in the area of transplantation. That is how Dolly the sheep, came about. Scientists have been trying to find a way to genetically engineer animals so that they can produce organs for humans that will not be rejected. Insulin from pigs has helped diabetics, pig valves can be used in cardiac repair, and pig skin helps burn victims,why not organs next ?

Pig 23 was genetically altered to incorporate human genes, in hopes of preventing rejection after transplantation. Pigs have organs that are about the right size and are similiar to humans, also the availability of these organs is great due to the reproductive cycle of pigs. The biggest obstacle is the issue of rejection. The new organ is typically killed, even before the surgeon closes the incision, due to hyperacute rejection. This process clots the blood, by forming antibodies that attach to the endothelium of the blood vessels in the organ. The complement system creates gaps in vessels, allowing gaps to form and clots to accumulate. Therefore, a complement inhibitor was developed as the gene was cloned, introduced into pigs whose cells produced this protein. Another thing discovered, was that the cells lining the pig vessels have a sugar molecules called alpha-galactose, and humans have lots of antibodies against alpha-gal. Some are thinking of knocking out the gene for alpha-gal and replacing it with the human gene for type O blood sugar. One other stumbling block may be the transferense of unknown virus’s like the HIV virus, that was somehow transmitted from monkeys. Scientists are hoping that most virus’s will not be viable in humans.

Tissue engineering is a promising new field and livers are being grown in sponges, in hopes of providing livers to those whose livers have failed.

Transgeneic production is providing large quantities of drugs at lower costs through the milk of female offspring. One product thay are looking at producing is human serum albumin(HSA). Another product is recombinant human antithrombin III (Rh AT III), which competes with plasma-derived AT III, an anti-clotting drug, the former being produced in goats milk.

The company who cloned Dolly, has 147 sheep now, and is working on production of alph-1-antitrypsin (ATT) which is a cystic fibrosis treament. They have been given permission to expand their flock to 10,000 sheep to manufacture ATT. Polly has appeared now, carrying the gene for human blood factor IX. “Pharming” also produces Protein C in pigs milk, which is used during a stroke or heart attack. Another exciting development is the production of human fibrinogen, which controls bleeding and is being sprayed on shark bites, for example.

Inserting genes has been accomplished to produce human lactoferrin in cows milk, from a founder cow named Herman, who sired a lot of females, carrying this gene. Lactoferrin is used in the intestines of immunocompromised patients to treat GI infections.

Who started all this genetic alterations? Mice. They were the first ones to possess altered genes similiar to cancer genes in human. Mice were engineered to be super smart and one mouse was called Doogie, suggesting that intelligence is alterable. Some think that this technology can be used for memory problems, like in Alzheimer’s patients. Others think that it will only be available to the wealthy, like cosmetic surgery, if used to boost intelligence. Scientists have also found a way to track gene placement by using the technology available from fireflies. Luciferase is use as an indicator light to monitor gene therapy, and may be helpful in transferring healthy genes into people with cystic fibrosis.

On a molecular level, transgenic mouse models have been used to study the specific genes of the skin, and the goal has been to target transgene expression in defined cells in cutaneous epithelium. LacZ reporter transgenes were used to test two enhancer/promoter sequences for expression in the skin of adult mice. A CMV enhancer/CMV promoter is not active in most cell types but a CMV enhancer/ modified B-actin promoter sequence is active in the suprabasal and basal cells of the epidermis as well as in the epithelial cells of the hair follicles, sebaceous glands, and dermal papillae. These models have been developed to help identify diseases of the skin.

In the corn field, scientists have been trying to find ways to keep pests and diseases from ruining crops as well as trying to increase the yields of plants. One thing that has been contoversial has been the formation of sterile seeds. This would create a monoply for the seed makers as well as cause difficulties for the poor farmers who save their seeds, even though the dangerous viruses in them would be eliminated. Genetically modified crops have included tomatoes, yogurt, cheese, and some vaccines, and more recently, soya and maize. Some feel that these products should be identifiable to the consumer at every level.

Some agricultural products are being used to produce enzymes, antibodies, and other biopharmaceuticals. One company is using corn to poduce monoclonal antibodies, which is about 25-100 times cheaper than comparable products in mammalian cell culture. Some other things that are in production of an antibody to block herpes transmission and contraceptive anti-sperm antibody. It appears that there is news of a class of antibodies that can deliver drugs to diseased tissue linings, which will help cystic fibrosis patients. Another company is developing antibodies that can stimulate an immune reaction against cancer cells in patients with non- Hodgekins Lymphoma, in mice it has cured the cancer. There is also work on enzymes that will treat lipid metabolism disorders.

Many are excitited about the creation of the purple petunia. This transgenic product was created by putting a bacterial gene into a petunia- launching the age of agricultural biotechnology. The Agrobacterium tumefaciens typically injects it’s DNA into the host, after the disease carrying genes had been removed, and then the newly spliced genes were introduced into the plant. This gene splicing divides the time needed for a new variety in half. What is interesting is that scientists have experimented with introducing genes from trees, bacteria, chickens and even flounder into corn, cotton, soybeans, tomatoes, potaotes and other plants. Many products on the market have been engineered to produce their own insecticide, thanks to a bacterial gene, or to tolerate popular herbicides. To be really effective, in terms of drought or growth rate, scientists must learn to splice whole sections of genes.

Here is a simplified outline of how the Agrobacterium splicing works:

1. A plasmid is removed from the agrobacterium.

2. The plasmid is snipped open and the desired gene is inserted. The plasmid is reinserted in the agrobacterium.

3. This agrobacterium is placed into a petri dish with plant cells, the agrobacterium latches onto one of the cells and and transfers the new gene into the cell’s DNA.

4. When the plant cell divides, each offspring recieves the new gene.

Trees that have been genetically altered have created their own controversy. The removal of lignin, the most expensive part of paper production, is being experimented with. This same component, lignin also gives the tree rigidity and toughness in the environment. Not to mention, the lignin breaks down slowly, during the rotting process, which is essential for all the plants and animals who survive on this process. The low content of lignin would provide fast food for those herbivores. The longevity of forests and their impact on the enviornment would be forever disturbed if trees were changed significantly. Industry is pouring about 60 million dollars into this research. The poor may benefit from genetic engineering, as it seems possible to increase the caloric content of wood providing more heat, but unrealistic to think that the developers will give the technology away.

A final note is about butterflies. Monarch butterflies that were found to have eaten the pollen from genetically altered corn, a pest resistant variety, which killed or stunted the growth of the caterpillar. This is due to splicing Bacillus thuringiensis into the corn. Many say the pollen will not be blown far enough to affect the butterflies. Another possibility to be concerned about is that these genes can be picked up by wild species and transmitted in that plant.

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