Animal pharming
Using animals as bioreactors is also cost-effective and advantageous because animals naturally carry the cellular mechanisms needed to produce complex proteins. Genes require certain cellular mechanisms to help them produce proteins. These mechanisms are present in a living animal, but they may be difficult or impossible to replicate in a cell culture. Animal pharming, the process of using transgenic animals to produce human drugs, is staking its claim in a lucrative world market. Transgenic animals are animals which have been genetically transformed by splicing and inserting foreign animal or human genes into their chromosomes. The inserted gene, when successful, enables an animal to make a certain pharmaceutical protein in its milk, urine, blood, sperm, or eggs, or to grow rejection-resistant organs for transplant. Global demand continues to grow for human proteins and vaccines. These proteins serve numerous therapeutic purposes such as treatments for cystic fibrosis, haemophilia, osteoporosis, arthritis, malaria, and HIV. Transgenic animals can also produce monoclonal antibodies (antibodies specifically targeted towards disease proteins) which are used in vaccine development.
In 1998, less than 1% of the world supply of human therapeutic proteins came from production of recombinant proteins (proteins which are formed by laboratory manipulation of genes in plants, bacteria, or animals). That tiny percentage of overall Table: Pharming products currently in research and development
Animal
|
Drug/protein
|
U s e
|
sheep
|
alpha1 anti trypsin
|
deficiency leads to emphysema
|
sheep
|
C F T R
|
treatment of cystic fibrosis
|
sheep
|
tissue plasminogen activator
|
treatment of thrombosis
|
sheep
|
factor VIII, IX
|
treatment of haemophilia
|
sheep
|
fibrinogen
|
treatment of wound healing
|
pig,
|
tissue plasminogen activator
|
treatment of thrombosis
|
pig
|
factor VIII, IX
|
treatment of haemophilia
|
goat
|
human protein C
|
treatment of thrombosis
|
goat
|
antithrombin 3
|
treatment of thrombosis
|
goat
|
glutamic acid decarboxylase
|
treatment of type 1 diabetes
|
goat
|
Pro542
|
treatment of HIV
|
cow
|
alpha-lactalbumin
|
anti-infection
|
cow
|
factor VIII
|
treatment of haemophilia
|
cow
|
fibrinogen
|
wound healing
|
cow
|
collagen I, collagen II
|
tissue repair, treatment of rheumatoid arthritis
|
cow
|
lactoferrin
|
treatment of GI tract infection, treatment of
|
|
|
infectious arthritis
|
cow
|
human serum albumin
|
maintains blood volume
|
chicken,
|
monoclonal antibodies
|
other vaccine production
|
cow, goat
|
|
|
production, however, was valued at almost $12 billion, or 50 %, of the $24 billion global market for human proteins. A list of important recombinant proteins worked as bio harming in livestock for large scale production is given in Table.
As per a Financial Times article a herd of 600 transgenic cows could supply the worldwide demand of some pharmaceuticals, for example, human serum albumin used in the treatment of burns and traumatic injuries. With greater integration of computers into laboratory functions, molecular biologists have drastically reduced the time needed to identify and isolate genes. As gene sequencing has become increasingly automated, each known sequence is recorded and stored in a data base.
The genes for 2 different human blood clotting factors (VIII and IX) have been hooked up to sheep and pig regulatory sequences that causes expression in mammary tissue; after transformation of sheep or pig embryos, genetically engineered animals have been selected that produce milk with a large percentage of human blood-clotting factor. This protein can be isolated from the milk, purified, and marketed. Similarly, transgenic rabbits have been created that produce human interleukin-2, which is a protein stimulating the proliferation of T-lymphocytes; the latter play an important role in fighting selected cancers. Other human proteins that have been expressed in transgenic animals include: anti-thrombin III (to treat intravascular coagulation), collagen (to treat burns and bone fractures), fibrinogen (used for burns and after surgery), human fertility hormones, human hemoglobin, human serum albumin (for surgery, trauma, and burns), lactoferrin (found in mother milk), tissue plasminogen activator, and particular monoclonal antibodies (including one that is effective against a particular colon cancer). Animals mostly used for this work are pigs, cows, sheep, and goats. The amounts of milk needed to provide a national supply of these pharmaceuticals are really very reasonable. Assuming the animals produce 1 g of the protein per liter milk and one has a purification efficiency of 30% (that is, 30% of the protein is recovered in the pure sample), then a pig can produce 75 g of protein per year, a goat 100 g, a sheep 125 g, and a cow 3 kg. As the national need of blood- clotting factor IX is 2 kg / year, 1 cow/country can do the job. For other proteins the demand is larger (for example, for tissue plasminogen activator it is 75 kg/year and for human serum albumin it is about 1,000 kg/year), but nonetheless a limited number of animals is all one now needs to meet the national demand for pharmaceutical proteins that used to be astronomically expensive.