The new guinea pigs
If transgenic plants are here, transgenic animals can't be far behind. And they aren't. Scientists have been able to alter animals to make them produce proteins, grow bigger and faster, breed in different conditions and also serve as models to study diseases.
For instance, instead of using recombinant bacteria to produce pharmacologically important proteins, scientists have genetically engineered cows and sheep to produce these proteins in their milk. The UK-based Pharmaceutical Proteins Ltd recently developed transgenic sheep that secrete an enzyme, known as AAT, the deficiency of which in humans causes progressive lung degeneration. Present treatment involves deriving 200 gm of AAT from blood and is prohibitively expensive. Tracey, the most impressive of the transgenic sheep, secreted 1.5 kg of AAT in a single lactation. Similarly, sheep have been genetically engineered to produce more wool.
A 30-kg salmon or a 5-kg mackerel? Fish for the dining table are also being genetically manipulated in at least a dozen US labs to make them grow faster, bigger and more adaptable to aquacultural conditions. At the Memorial University in St John's New Foundland, scientists are trying to make salmon breed in sub-zero seawater by implanting them with "anti-freeze" genes from the flounder, a cold water-inhabiting fish. This would enable commercial fisheries to operate in waters too cold for normal salmon. Rat and human growth-hormone genes are also being incorporated into fish like rainbow trout, carp and tilapia to make them grow faster.
As yet, most of the transgenic animals produced have been restricted to the laboratory because a number of thorny ethical and regulatory issues still have to be ironed out.
The important breakthrough in transgenic animals is the development of genetically manipulated animals that can serve as models for several scientific studies. These animals help scientists to study developmental biology, immunology and genetic disorders. The demand for these animals is high, as are prices, and researchers are reluctant to part with their mice, especially to competing labs.
In 1988, the genetically engineered Harvard "onco-mouse" -- that carries a human cancer-causing gene -- became the first animal to be protected by a patent in the US. Offspring of the onco-mouse get cancer within months of being born, providing an excellent model for researchers studying cancer.
Last year, the cystic fibrosis mouse was hailed by medical researchers the world over. The cystic fibrosis mouse, which mimics many of the features of the human illness, has got researchers excited. But, says Tom Boat, a paediatric pulmonologist, "We do not have access to the lungs of little babies (in the early stages) of cystic fibrosis."
Scientists who developed this "knockout mouse" used a new gene-targeting methods to replace the cystic fibrosis gene in a line of embryonic cells, and then placed the cells into embryos which were placed in female mice to develop. The resulting mice, known as mosaics or chimeras, carry the mutant gene in some of their tissues and were then bred to produce knockout mice that have one copy of the altered genes in all their tissues. These can then be bred to produce offspring with two copies of the defective gene, which can then be studied for the effects of the gene.
Another knockout mouse, known as the SCID (severe combine immuno-deficient) mouse, has also been developed as a possible alternative model to the rhesus monkey to study AIDS in humans. Sickle-cell disease, beta thalassemia and Gaucher's disease are some of the genetic disorders that researchers are trying to recreate in knockout mice.
However, because of high prices -- as much as $150 a mouse -- these mice have not met commercial expectations. Du Pont, which holds the patent for the onco-mouse, has a steep fee structure and strictures that users find onerous. For example, users are expected to share revenue from a product developed by using the mouse as a model. Says Melvin Balk of the Charles River Laboratory in Massachusetts, which has entered into an agreement with Du Pont to maintain the mouse and distribute it commercially, "(The mouse) has proved to be a disaster from our perspective." He adds that most inventors "overestimate the value" of transgenic mice and need to be more "realistic".