A mouse click and Stefan Dübel presents “one of the most beautiful molecules in the world”. With a devout look, the biochemistry professor from the Technical University of Braunschweig rotates the 3D model of an antibody on his laptop monitor, an Y-like structure, colored gray and red. For tens of years he has been working on producing these complex protein molecules in the laboratory without animals having to suffer. “This dream has come true,” he says. The vegan antibodies have been sold by the start-up Abcalis for research purposes and medical tests since 2019. It recently won the Animal Welfare Award from the European Coalition to End Animal Testing.
Antibodies are vital tools of our immune system, they recognize and mark germs. They can also have a healing effect as active ingredients in medicines. And because they fit almost perfectly to the target molecule for which they were produced, they are also interesting for science. Peppered with dyes, they can help to make hormones or viruses visible, for example in pregnancy or corona rapid tests.
In Europe alone, more than a million animals bleed for the antibody industry every year
However, for the production of the potent biomolecules, hundreds of thousands of animals have had to be bled regularly to date. Above all, rabbits, mice and sheep are used for production. Exactly how many is unclear. In Europe alone there are more than a million animals every year, estimates a scientific body of the EU, which interviewed producers and viewed catalogues. On the other hand, according to the German initiative “Understanding animal experiments”, a maximum of one third of them is realistic, with reference to figures from the EU’s Alures database, which, however, also only allow indirect conclusions. The so-called mouse ascites method is particularly criticized. The antibody production in the spleen of mice is boosted by the administration of growth accelerators, according to the Alures database in the EU around 55,000 animals were affected in 2018.
As a student, Dübel got to know this special method of antibody production in internships. “The belly was almost bigger than the mouse itself. So we said: It doesn’t work that way. We’d rather draw the blood ourselves,” he says. After all, human blood contains innumerable genetic blueprints for antibodies that simply form randomly through mutations. “Antibodies that have never seen a pathogen swim in our blood,” says the researcher.
Together with a colleague, he collected blood samples from around 100 voluntary donors from all over the world, isolated antibody blueprints from them and stored them in a laboratory freezer at minus 80 degrees Celsius. “Today we have a DNA library with about ten billion human antibody genes. You just have to choose the appropriate ‘book’.” The “book” contains the genetic blueprint for antibodies, each capable of recognizing a selected molecular target.
The method used here is called phage display. The protagonists are viruses with special abilities, so-called bacteriophages. They convert the ten billion genetic blueprints from the antibody library into just as many different antibody surface structures. Now all that remains is to find the antibody that recognizes the desired target structure, the “antigen”. The company Abcalis, for example, provides this to the respective client. With the help of this antigen, the virus can be “fished out, so to speak,” with the right blueprint, says Abcalis Managing Director Laila Al-Halabi-Frenzel. The team finally smuggles the genetic information from the phage capture into cultivated human cell cultures, which, based on the genetic blueprint, begin mass production of the desired antibodies. The product is finally harvested, cleaned and bottled for the customer.
Currently, the animal-free antibodies cost about twice as much as those made from animal blood
There isn’t even a milliliter of antibody essence in the pencil-thin plastic tubes that the company sends out. “This small amount is worth 1,000 euros to our customers,” says Al-Halabi-Frenzel. Since the method is still new, the animal-free antibodies currently cost about twice as much as those made from animal blood. However, the antibodies from the cell culture not only have ethical but also qualitative advantages. “Our antibodies are chemically defined and can be reproduced at any time.”
The switch from animal to laboratory production is possible and necessary, it said in a 2019 report by the EU reference laboratory for alternatives to animal testing. This not only applies to the use of antibodies in diagnostics and research, but also in therapy. “However, this recommendation apparently did not reflect a differentiated scientific consensus, but was too one-sided and probably also politically motivated,” says Roman Stilling from the Understand Animal Experiments initiative. Criticism from scientific associations rained down and the industry. Restrictions or even a ban on animal-assisted antibody production would result in disadvantages for research and international competition, so the fears.
The Braunschweig biotechnologist Dübel, who was involved in the scientific part of the EU report, does not entirely agree with the derived recommendations either: “They were not agreed with us scientists, especially since our research had not even addressed the use in therapy.” However, he believes that the critics’ fear of a ban is exaggerated. “There are currently not enough synthetic antibodies available for a switch,” he emphasizes. In order to give the matter a boost, its advantages would have to become even better known. After all, some companies already offer antibodies from animal blood as well as synthetically produced ones. “Both processes should compete with each other in terms of quality,” says Dübel. “Then research will not be hindered, but will gain new opportunities.”