Animal Welfare Prize for Max Planck researchers

The prizewinners have developed an alternative to the most widely used antibodies, which can drastically reduce the number of animals in antibody production

Dirk Görlich and Tino Pleiner of the Max Planck Institute for Biophysical Chemistry in Göttingen have been awarded the Animal Welfare Prize of the Federal Ministry of Food and Agriculture. The two scientists recently succeeded in developing secondary nanobodies, which can replace conventional secondary antibodies. The latter are widely used in medical diagnostics and basic research and are produced on an industrial scale in large laboratory animals such as goat, sheep, or donkeys. The researchers’ invention can thus drastically reduce the number of animals used for antibody production.

“We are thrilled to have developed a technology that bypasses the use of numerous experimental animals. As animal welfare is close to our hearts, we are really pleased to have received this important prize,” says Dirk Görlich, Director and head of the Department of Cellular Logistics at the Max Planck Institute for Biophysical Chemistry.

The natural function of antibodies is to fight infectious diseases. They are, however, also indispensable tools for biomedical research and diagnostics. Pregnancy tests, blood groupings, or many kinds of histological examinations, for example, are based on antibodies that recognize a diagnostic target molecule, also called an antigen.

A typical setup is a two-stage detection with primary and secondary antibodies. Primary antibodies bind the antigen, for example a tumor marker. Secondary antibodies, in turn, are coupled to labels that emit signals such as fluorescent light and bind the primary antibodies. Thereby, they can make the antigen of choice indirectly visible within cells or tissues. This indirect way of detection is highly modular, that is one batch of labeled secondary antibodies can be used to detect millions of different primary antibodies and thus a very large number of different antigens. This implies that secondary antibodies are produced at far larger scales than any primary one.

The first step in antibody production is injecting a purified antigen into an animal. The animal’s immune system then produces antibodies against the antigen. Finally, the antibodies are collected from the animal’s blood and prepared for use. This procedure is not only time-consuming and expensive but also poses an ethical problem, as the enormous demand for antibodies worldwide means that animals have to be sacrificed in large numbers.

Bacteria instead of experimental animals

Dirk Görlich and Tino Pleiner, a former PhD student in Görlich’s lab, have now created a sustainable substitute for secondary antibodies in the form of nanobodies. These are fragments of mini-antibodies with particularly simple structures that are obtained from camelids such as alpacas. The animals deliver here just the “construction plans” for the antibody-substitutes; the following production then a complete animal-free biotech process.

“As with conventional antibody production, an alpaca is first immunized with a purified antigen. But here, the immunization can be mild, because there is no need to force the animal to make large amounts of antibodies. Getting a few good blueprints is enough,“ Görlich explains.

“The next step is to take a small volume of blood and to extract and sort the construction plans. Such blood sample contains blueprints for millions of different nanobodies. The challenge here is to find plans for really well-performing secondary nanobodies. These are then used to instruct bacteria to produce the desired secondary nanobodies on any scale and as often as necessary. So, we can outsource the nanobody production completely – to microorganisms instead of mammals,” Pleiner emphasizes the importance of the team's work. “This technology has the potential to drastically reduce the number of animals used for antibody production and to make a major contribution to animal welfare in research.”

As Ulrike Teichmann, head of the Animal Facility, points out, the immunization applied here to the alpaca is comparable to a human vaccination and harmless to the animal. In fact, the procedure causes the animals so little stress that one animal can provide material for several nanobody projects while enjoying a high quality and long expectancy of life. “These are particularly important aspects of animal welfare,” adds Sarah Kimmina, the responsible Animal Welfare Officer.

Better performance in the lab

It is not only their contribution to animal welfare that makes nanobodies such a valuable alternative to antibodies. In standard laboratory applications, they are at least as useful as conventional antibodies and may even outperform them: “Nanobodies are about one-fifth the size of antibodies. For example, when they are used in fluorescence microscopy, they allow for sharper images and better resolved cellular structures,” Pleiner reports.

“Apart from microscopy, we have already tested secondary nanobodies in other applications, and the results are very promising,” Görlich stresses. “We are confident that our nanobodies will replace conventional secondary antibodies raised in mammals such as donkeys, goat, or sheep and will make antibody production in these animals largely obsolete.” (ad/cr)

About the prize winners

Dirk Görlich studied biochemistry in Halle (Saale) and was awarded a doctorate by the Humboldt University in Berlin in 1993. After a two-year research stay at the Wellcome/CRC Institute in Cambridge (UK), he was appointed Research Group Leader in 1996 and Professor of Molecular Biology at the Center for Molecular Biology of the University of Heidelberg (ZMBH) in 2001. He is heading the Department of Cellular Logistics at the MPI for Biophysical Chemistry since 2007. Görlich is the recipient of numerous scientific honors, including the Heinz Maier-Leibniz Prize, the EMBO Gold Medal, and the Alfried Krupp Prize for Young University Teachers. He is a member of the European Molecular Biology Organization (EMBO) and the German Academy of Sciences Leopoldina.

Tino Pleiner performed undergraduate research in biochemistry in Leipzig and then entered the MSc/PhD program at the International Max Planck Research School for Molecular Biology in Göttingen. For his doctoral thesis, he spent four years carrying out research in Görlich’s Department of Cellular Logistics at the MPI for Biophysical Chemistry. In 2017, after being awarded his doctorate, he moved to the California Institute of Technology (Caltech) in Pasadena (USA) for postdoctoral research.