Animal Pharming - PART 2

E. Some Pharming Projects of Interest

When the Roslin Institute and PPL Therapeutics announced the birth of Dolly in 1996, quite a stir was created. Dolly, a sheep, was the first animal cloned from an adult cell, previously believed to be impossible. A year later, the same group announced the birth of two more cloned sheep, Molly and Polly. However, these two sheep were very different from their cousin, Dolly. The most pronounced difference was the fact that they both carried the human gene that codes for a protein called Factor IX. Factor IX is a blood clotting protein, and it is commonly used to treat patients that have hemophilia B, a disease that is caused by a deficiency in Factor IX. The goal of creating Molly and Polly was to produce a herd of sheep that produced Factor IX in their milk. The only other source of Factor IX is from human blood plasma. By producing Factor IX in sheep milk, it is hoped that the cost of production will be greatly reduced.

Advanced Cell Technology, Inc is using the queen of milk production, the cow, for potential use as bioreactors. They have produced transgenic cows that secrete the protein serum albumin in their milk, a protein that is used to extend blood volume and is used in patients suffering from traumatic injuries, such as burns. Cows are an obvious choice for pharming purposes as they can produce upwards of 8000 L of milk per year, and an estimated 40 to 80 kg of protein a year. That is quite a substantial amount compared to the 4 kg of protein per year in goats and 2.5 kg of protein per year in sheep.

One interesting project is that taken up by Nexia Biotechnologies. For years humans have wanted to employ the silk of spider webs for many applications, as the silk is strong, elastic, and extremely lightweight. However, unlike silk worms, spiders cannot be farmed for their silk, as spiders are extremely territorial, plus it is not the complete web that is desired, rather a portion of the web referred to as frame silk. Cell cultures have been unsuccessful for producing spider silk, as they tend to produce fibres that are too short for commercial applications. Nexia Biotechnologies has been successful at producing spider silk in the milk of goats, and is in the process of developing "Biosteel®", a man made fabric made of spider silk. Potential applications of this fabric are extensive, ranging from medical uses (wound closures, dressing, patches, glues, prosthetic devices), to military uses (strong, light-weight body armour), to sporting goods (biodegradable fishing line).

F. Commercial Products from Animal Pharming

The technology used to develop transgenic animals is somewhat mature, however, the industrialization of bio-pharming is new. The first transgenic animal, a mouse, was produced in 1981. In an effort to determine which genes were involved with cancer, a gene was inserted into the mouse that made it susceptible to cancer. In 1985, the first transgenic farm mammal was produced, a sheep called "Tracy". Tracy had a human gene that expressed high levels of the human protein alpha-1-antitrypsin. The protein, when missing in humans, can lead to a rare form of emphysema.

There are a number of products that are available commercially that are produced from animal pharming. An even greater number of products are being developed in order to lower the cost and greater efficacy.

A number of products with specific therapeutic value have been incorporated into the commercially available animal pharming pharmaceuticals and products. A number of
companies are actively involved in the research and production of useful products from transgenic animals.

G. Ethical Issues to Pharming

Many of the ethical issues that arise from pharming surround the treatment of animals. Even with the 100% transgenic offspring produced by nuclear fusion, many are born with birth defects and gross abnormalities or do not produce the protein of interest. Additionally, while 100% of the animals born are transgenic, a large number of eggs are used in the process of finding one can be implanted. This in itself may not be too alarming, however, most of the time the egg "donor" is slaughtered in the donation process.

Another issue is the idea of the age of the clones. Dolly recently passed away at the age of 6 and a half. Considering that the average sheep lives for 11 to 12 years, this was quite young. Dolly died from a lung disease found only in old sheep, adding to speculation that cloning animals may affect their age. In fact, many cloned animals tend to die young, some within weeks of birth. When the Roslin Institute and PPL Therapeutics announced the birth of Molly and Polly, they had a litter of six lambs out of 14 cloned embryos. One died within hours of birth, and three more died shortly after, leaving the world with Molly and Polly.

Finally, as transgenic animals are being produced, biotech companies are quick to patent their work in order to maximize their profits. This raises the issue of animal rights, and whether or not these animals will be treated as sentient beings or whether they will simply be treated as walking factories.

Using transgenic animals as a source of pharmaceutical proteins raise minor general bio safety and ethical problems. Indeed, the escape of the animals in environment is extremely unlikely and in the majority of the cases, animals do not suffer from expressing a foreign protein in their milk or eggs. Several proteins raised specific problems. Human erythropoietin produced in rabbit milk altered their health. Less intense side effects were observed when human growth hormone was produced in rabbit milk and the high producers of human EC superoxide dismutase failed to lactate in a normal way [unpublished data].

The number of companies involved in the production of recombinant pharmaceutical proteins is expected to increase. This will result from the improvement of the different systems and from the fact that the oldest patents are becoming obsolete in the coming years. Competition may thus become very intense. Some experts consider that the demand of pharmaceutical protein production might increase faster than the capacity of the companies to produce proteins. The different systems would be then all helpful for one or two decades.

H. Conclusion

Pharming promises a world of cheap pharmaceutical drugs, new medical applications and many other products with potentially diverse applications. As transgenic animals, pharming, and cloning become more mainstream, a small yet growing portion of the animal production industry will shift its operations from farming livestock for meat production, to pharming transgenic animals for pharmaceutical production. The world market is growing for human pharmaceutical products. Producing transgenic animals is still relatively expensive, however, costs are trending down and transgenic animals have certain advantages over traditional laboratory methods for producing human proteins. More commercial use of transgenic animals in food production is also likely.

The Scientific community in general agrees that, regulators will need to review existing policies and guidelines regarding transgenic animals. New policies regarding transgenic and cloned animals may be necessary to ensure the safety and health of humans and animals. Ongoing public debate regarding transgenic technologies will ensure that further research and analyzes will be demanded by animal producers, regulators, environmentalists, and the general public.

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Animal Pharming - PART 1