Farmaceuticalsby Cyrus Ance
Farmaceuticalsby Cyrus Ance
Transgenic animals (1) are not new. Genes were first inserted into mice nearly 20 years ago. Besides the scientific uses of this technology a recently opened frontier is the production of therapeutic proteins and hormones in transgenic animals. The basic idea is to find a gene for the production of a useful protein or hormone, insert it into cells, grow them, and harvest the output.
There are some problems besides the non-trivial effort it takes to find, isolate, and insert the genes. Cells are not the best means of production. Often the most useful products can only be produced by mammal cells rather than yeast or other comparatively simple to grow types. In any case growing and caring for cells is expensive in terms of both materials and trained personnel. Perhaps the biggest problem is that once a transgenic cell culture is up and running it is neither cheap nor easy to expand production. This can be devastating if either the production level or effectiveness of the product is lower than expected. The cost to develop a cell based production line for a protein or hormone today is about $250M. Even at dot.com capitol burn rates a failure or less than complete success is likely to be fatal.
Thus the idea of producing transgenic farm animals to produce therapeutics, dubbed farmaceuticals. Cows, for example, naturally produce protein rich milk, their care is not particularly expensive and does not require highly trained personnel, and it is easy, although time consuming, to scale up production once the technique is shown to work.
Cattle and goats are among the best candidates since they produce milk in large amounts and it is pretty straight forward to extract a specific hormone or protein. Sheep and pigs have also been used, but their milk production per animal is much lower than cattle or goats. The cost is not cheap, about $100M, but the prospects to expand production after an initial demonstration are much better than cell based production (2).
A race is on to successfully demonstrate the technique in chickens. Especially delicate products, because they are destroyed by light for example, which are not suitable for extraction from milk could be contained in the safe environment of chicken eggs. Many plants, tobacco and corn a favored choice, can produce useful levels of proteins and thus there are active efforts to produce therapeutics in plants. A successful plant transgenic could easily be mass produced.
Two things hold back farmaceuticals from becoming more widely used. The first is the basic problem of the unpredictability of the production level of the product. We can insert the gene for production of a certain protein into an animal but we have little control over how the gene is expressed and thus how much of the protein appears in the milk. The process at the moment is hit or miss. Second is the time factor. It takes time, years for cattle and sheep, for animals to mature until their products can be harvested at production levels. Chickens and plants have a big advantage here. The combination of uncertainty and long time cycles has served to stifle the industrial production of farmaceuticals.
Reliable cloning would be a big boost to farmaceuticals. Successful animals, those that had high production levels of a therapeutic, could be duplicated by cloning much easier than current methods. Cloning would make it fast and predictable to expand a transgenic herd or flock to economically viable levels.
2 - There is a good article from BioPortfolio.com, a biotechnology guide, on the real state of therapeutic production in transgenic animals today. There is an excellent article in the 14 December 2002 Economist which focuses on the work of GTC Biotherapeutics . Unfortunately the online version of the article is for subscribers only.