Biotechnology: Animals as drug reservoirs

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Biotechnology: Animals as drug reservoirs
Biotechnology: Animals as drug reservoirs

Animals as drug reservoirs

Transgenic goats give healing milk, transgenic hens lay eggs that are processed into cancer drugs. Biotechnology has recognized the potential of animals as bioreactors for therapeutic agents and is eagerly exploring new applications. But what are the real benefits of "gene pharming"?


The scientists at the Roslin Institute in Scotland seem to have pulled off another coup. They have succeeded in breeding a flock of chickens that secrete proteins in the albumen of their eggs to treat cancer and multiple sclerosis. To do this, they smuggled appropriate foreign gene sequences for the desired substances into the genome of the poultry. This resulted in around 500 chickens that now lay eggs with therapeutically effective proteins every day - depending on the chicken and egg between 3.5 and 426 micrograms per milliliter [1].

However, it is still unclear whether and when the active ingredients from the egg will benefit patients. Because before a new drug can be launched on the market, there are many costly tests and studies. Nevertheless, the researchers are satisfied with their performance. After all, it is not every day that successes are reported in the field of "gene pharming".

The symbiosis of pharmacy and animal husbandry

The neologism "gene pharming" or molecular pharming links the term pharmacy with the English word "farming", and thus hits the target of this area of biotechnology pretty much exactly: With the help of genetically modified livestock or plants you want to Simplify the manufacture of pharmaceutical products by allowing the animals or plants to incidentally produce those active ingredients that are difficult or very expensive to produce using industrial processes.

In Germany, the Gene Center of the Ludwig Maximilians University in Munich and the Institute for Animal Breeding and Animal Behavior of the Federal Research Center for Agriculture in Mariensee near Hanover are particularly active in research with transgenic animals. And pharmaceutical companies and research institutes are pinning their hopes on animals of this kind: a single cow, wrote Johannes Schenkel from the German Cancer Research Center in Heidelberg hopefully in a 1995 book about transgenic animals, could produce around ten kilograms of a therapeutic protein in its milk every year. Depending on the active substance, this is more than is actually needed every year.

Animals as inexpensive medicine carriers?

To achieve such yields, however, researchers must first create animals equipped to produce therapeutics. And here the problems begin. Because the methods of gene transfer are anything but mature. In fact, the researchers only have to introduce certain alien gene sequences into the fertilized egg cell of the respective animal.

In theory, there are also sophisticated methods for this, for example by using deactivated viruses as means of transport, which then dock onto specific areas of the DNA and exchange gene sections. In reality, however, the experiments are like playing the lottery: the foreign sequences are correctly integrated in a maximum of 30 percent of the transgenic embryos. A few years ago, the success rate was a meager one to five percent. In addition, not all transgenic embryos really mature into he althy animals later [2].


Whether these then have the properties desired by the researchers is a completely different question. Only a few transgenic animals later actually release the desired substances into their milk, for example. The success rate is between one and ten percent. And the breeding of transgenic herds is still difficult: out of one hundred descendants of transgenic goats or sheep, only a maximum of twenty inherit the ability to produce medicines. With Mendel, the rules of the game of genetics seemed simpler.

The yields are also extremely different depending on the animal. Breeding in which attempts were made to cross very productive animals with one another failed miserably. The cost of producing a transgenic calf is estimated at around 400,000 euros, a whole herd would probably cost well over ten billion euros [3].

Nevertheless, research on transgenic organisms is considered an important mainstay of modern biotechnology. Because once it has been possible to breed a transgenic herd, the proponents say, the further costs are low and the work is also limited. In addition, milking the animals or laying the eggs of the hens is not painful, and ethical complications remain low. But the image of happy transgenic farm animals living peacefully together in their farm community is naïve: "The pharmaceutical husbandry of transgenic animals cannot be compared to that of normal agriculture," says Bärbel Hüsing from the Fraunhofer Institute for Systems and Innovation Research.

The Risk of Disease Transmission


Finally, it must be avoided that animal diseases such as BSE and scrapie or viruses are transmitted to the human beneficiaries. Because theoretically, any infection of the animals could also affect the recipients of their medication. "Just imagine what would happen if transgenic chickens got bird flu," explains Hüsing, adding: "The animals and their surroundings have to meet very high hygiene standards." However, such a germ-free environment has little in common with species-appropriate husbandry.

Strict standards must also be observed for transgenic plants that produce pharmacological substances. Neither plants nor pollen may get into the environment or even onto your plate. "These security measures represent costs that are often not considered," explains the scientist.

Despite the many problems, "gene pharming" has had some successes over the decades. The best example is the first drug that was produced with the help of genetically modified organisms: insulin. Until the 1980s, the hormone that is vital for diabetics was extracted from the pancreas of cattle and pigs. But in 1982, an improved variant was successfully cultivated in genetically modified Escherichia coli bacteria. This method is now the standard in insulin production.

From bacterium to dairy cow

Since this breakthrough, prokaryotes have served as frugal and low-maintenance suppliers of medicinal agents. Most of the recombinant proteins are produced by such microorganisms, and more than 60 corresponding drugs are already on the market. However, the tiny pharmacists are only useful if the active ingredients consist of simple, short-chain proteins. Because the bacteria or even yeasts cannot synthesize more complex structures themselves with foreign genes.

But since many diseases such as hemophilia A, the most common form of bleeding, require more complex proteins for treatment, the pharmaceutical industry devised so-called bioreactors. Here, human or animal cells that produce certain active ingredients are cultivated with great effort. Since the mid-1990s, hemophiliacs have been able to be supplied with recombinant factor VIII in this way. Previously, this had to be painstakingly obtained from human plasma. But the industrial bioreactors are expensive, and the production of medicines with them takes a long time. The hopes for animals as drug reservoirs are therefore high.

Transgenic animal and plant research is not as dynamic as scientists would like us to believe

(Bärbel Hüsing) A good fifteen years ago, scientists succeeded for the first time in producing a transgenic farm animal that gave milk that can be used for medical purposes: Tracey the sheep produces large amounts of human antitrypsin, the deficiency of which can cause serious organ damage in humans. Since then, there have been experiments with almost every known domestic animal: mice, rabbits, goats, pigs and cattle were created in the test tube and genetically manipulated.

As early as 2000, around 300 recombinant drugs were being tested in clinical trials, and hundreds were in development. According to research by the Association of Research-Based Pharmaceutical Manufacturers, there are currently 89 active ingredients in Germany that have been manufactured using genetic engineering. In 2005, they accounted for almost ten percent of drug sales in German pharmacies.

Two years ago, however, not a single approved drug came from the udder of transgenic animals. Only last year, the first active ingredient from goat's milk was approved in Europe: The company GTC Biotherapeutics received approval for an antithrombosis drug for patients with a hereditary deficiency in the body's own antithrombin. "Research in the field of transgenic animals and plants is not as dynamic as the scientists would like us to believe," explains Hüsing.

She doesn't believe that transgenic animals or plants are much better than the methods used to date. "Depending on the desired protein, all three production platforms have their advantages and disadvantages," she says. In order to avoid the transmission of diseases, for example, plants are better suited. However, they often do not have the precise protein folding that makes the molecules effective in humans. And the conventional method of growing cells in the laboratory is laborious, but it is tried and tested and comparatively safe.

Ultimately, the future would have to show whether transgenic animals would really play a role in drug production. "At least I don't know of any particular advantages of using transgenic animals," she says.

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