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Brave new world of farmaceuticals

(Wednesday, Dec. 18, 2002 -- CropChoice news) --

The Economist, 12/14/02:HUMANS never tire of hearing tales of heroic animals. Fables abound of people owing their lives to a St Bernard or a horse. In the near future, however, an entirely different breed of creatures could be saving humans in distress. Imagine owing your life to a goat, cow or chicken? Welcome to the brave new world of farmaceuticals. Biotechnology firms are busy trying to turn humble barnyard animals into living bioreactors full of life-saving medicines. Through the process of genetic modification, such animals can be induced to produce large volumes of certain proteins in their milk, eggs or blood. And when purified, such proteins can be used to treat diseases.

Drug makers are especially keen to get their hands on large quantities of compounds known as monoclonal antibodies. These proteins, which act as the footsoldiers of the immune system, recognise and bind to alien objects in the body. Drugs made from antibodies could take aim at bacterial infections, perhaps even cancerous cells, far more accurately than synthetic drugs. Since drug makers can simply isolate antibodies, and the genes that code for them, from the blood and cells of laboratory animals, they can avoid having to design therapeutic molecules entirely from scratch. For decades, medical researchers have dreamed of making these "silver bullets" into drugs. But even silver bullets must be formed in some sort of foundry. And makers of therapeutic proteins--"biopharmaceuticals", as they are known--desperately need more foundries if they are to bring them to market in commercial quantities.

A mere ten antibody drugs now absorb nearly all the antibody production facilities in the world. When demand recently exceeded supply for Immunex's new antibody-based drug, Enbrel, the company had to persuade another biotechnology firm, MedImmune, to part with the "production slots" it had reserved at Boehringer Ingelheim, a contract drug manufacturer based in Germany.

The other option--to build a new facility to produce such compounds--would have cost $200m-400m and taken three to five years to complete. Such outlays deter cash-strapped drug makers, especially those requiring only small quantities of a protein to complete a series of clinical trials and win regulatory approval.

If manufacturing biopharmaceuticals in animals could be made more efficient, it would overcome the logjam that has been holding a flood of new therapeutic compounds back. More than a hundred protein-based drugs are now in advanced phases of clinical trials, and many more are in development in the laboratory. The stakes are high, in terms both of lives that might be saved and profits that might be pocketed. If manufacturing in animals can be made a success, it will bring drug makers and biotech firms billions of dollars in sales over the coming decade.

At present the most advanced technology for biomanufacturing involves goats and cows. At GTC Biotherapeutics in Framingham, Massachusetts, scientists are capitalising on the benefits of natural selection. Over the ages, the mammary glands of goats and cows have evolved to pack proteins into breast milk--so that mother animals can nourish and protect their young. When a goat is genetically modified to carry a gene for a therapeutic protein, the breast cells treat that gene like any other. So far, GTC Biotherapeutics has successfully engineered goats that excrete 14 varieties of therapeutic protein in their milk.

A firm wishing to produce a therapeutic protein in quantity can contract GTC to create transgenic goats that excrete the desired protein in their milk. According to Thomas Newberry of GTC, creating a herd of transgenic goats costs about $100m--expensive, but still only a third the cost of building a protein production facility. Moreover, when a drug maker needs to double production, it simply breeds more animals--thereby avoiding spending $300m on a new factory.

Mr Newberry reckons it takes about 18 months to make a transgenic goat that produces a desired therapeutic protein in its milk. To reach the same point in a cow requires about three years. Once the transgenic mammal has matured, however, increasing the volume of protein production is simply a matter of milking. Goats produce roughly two litres of milk a day, while cows produce about 20 litres a day.

How much the purified protein will cost is uncertain. The traditional method of production for such proteins, which involves culturing large volumes of mammalian-derived cells and extracting their contents, costs about $150 a gram. By using goats and cows, Mr Newberry estimates that his firm may be able to produce raw protein for $1-2 a gram.

Other firms are turning to chickens to achieve the same results. Chickens have some advantages over goats or cows. First, chickens lay eggs which, like Tupperware, are sterile, sealed containers for protecting and storing delicate contents. The albumen, or egg white, is an ideal place to store fragile compounds. Second, chickens are quicker to mature and cheaper to breed than goats or cows. A chicken flock can multiply tenfold within a year. And each additional bird requires only one square foot of extra space in a chicken coop.

Despite the attractive economics, however, research into transgenic chickens is not as advanced as research into goats or cattle. In July 2002, TranXenoGen, an avian transgenics firm based in Shrewsbury, Massachusetts, announced that it had produced two antibodies--one human antibody and one mouse antibody--in the albumens of so-called "chimeric" chickens, which produce the desired protein in some (but not all) their cells. However, the yields of these proteins were quite low. It could be another year or so before TranXenoGen produces fully transgenic chickens with a higher yield of therapeutic protein in their eggs. At present, TranXenoGen is aiming to produce transgenic chickens that make eggs containing insulin and human serum albumen, with an eye on getting regulators to stamp their seal of approval on drugs produced this way.

Many other biotech firms are rushing to turn farm animals into protein factories. Others are trying to do the same with crops such as corn and alfalfa. However, two big hurdles remain. First, the firms have to get regulatory approval for these products. More important, they must soothe public fears about the risks of cross-species infection, such as bovine spongiform encephalitis ("mad cow disease"). But if these obstacles can be surmounted, then some animals in the farmyard of the future will indeed be more equal--and certainly more helpful--than others.