From waste removal to the Nobel Prize

Research is global and cooperation beyond country borders is essential. Almost nobody knows this better than Nobel laureate Aaron Ciechanover.

Cells are the smallest units of life. And the core of life is cooperation: Minute by minute, billions of protein, fat and sugar molecules interlock in millions of perfectly coordinated chemical reactions to maintain that which constitutes life. Perhaps this is why Aaron Ciechanover understands so well why international cooperation between researchers is so important. “Cooperation does indeed bring science to life.” This researcher and Nobel laureate of the Technion University in Haifa decoded one of the most important cooperation processes in the life of cells: The way the cell removes waste.

Cienchanover’s first German cooperation partner was Dieter Wolf, currently at the Institute of Biochemistry at the University of Stuttgart. This was at the end of the 1970s and Ciechanover had already discovered (in conjunction with his doctoral supervisor Avraham Hershko and the US researcher Irvin Rose) that the cell marks defective or superfluous protein molecules.

Portrait von Aaron Ciechanover der mit verschränkten Armen vor einem Baum steht und den Betrachter anblickt
    photo: Aaron Ciechanover

A small protein fragment, called ubiquitin, attaches to the proteins and serves as a signal to the cleaning staff of the cell (like the “green dot” on German packaging waste): “This can be removed.” These marked proteins are then fragmented and the individual parts, the amino acids, are recycled to build new protein. The ubiquitin systems play a role in the development of cancer, neurodegenerative diseases like Alzheimer, as well as in the design of new pharmaceuticals, and researchers need to take this into consideration for new medication to work. If the protein waste is not removed from the cells, it accumulates, for example, in the neurons in the case of Alzheimer, and gradually poisons them. These cells usually die, but when the waste removal does not remove enough of the proteins that support cell division, cancer can develop.

When new active substances are developed, pharmacologists have to develop the new medicine in such a way that the ubiquitin signal can either be attached to it or not – depending on how long it should stay in the cell and be effective.

The ubiquitin process is so essential for the cell that nobody was surprised when these three researchers were awarded the long-awaited Nobel Prize for their discovery in 2004. Previously, many research groups had also worked together in Ciechanover’s laboratory. During the past years, the funding programs of the German-Israeli Project Cooperation (DIP), the German-Israeli Foundation (GIF), the Volkswagen Foundation, the Minerva, and the DKFZ-MOST programs have facilitated various knowledge exchanges between Ciechanover’s laboratory and German researchers. “They have always been very supportive of our work.”

Whoever asks the proud Israeli whether he, due to German history, ever has concerns when working with German researchers, receives a decisive “no” as an answer. “Science is the future, and even if history remains part of our collective memory, we can nevertheless look forward.”

At the moment Ciechanover works closely with Thomas Sommer, the biochemist and interim head of the Max Delbrück Centre in Berlin-Buch. “We examine how mammal cells discard defective proteins,” says Ciechanover. “In Berlin, the same process is examined in yeast cells and we can study the similarities and the differences, thus increasing our knowledge.” This is not only about the exchange of reagents and cells, but especially about students who can, either in Berlin or Haifa, learn the respective special techniques by which the researchers can decode the mystery of protein waste removal. But cooperation is not only about learning new techniques. It is also about getting to know each other, to speak another language, to understand another history, and to experience another way of thinking, music, and culture. “This shapes personality and broadens the horizon.” This is important, because: “Research is always international, and therefore there is no such thing as Israeli or German research.”

The “most important prerequisite for research” is curiosity, a universal human characteristic. “Without curiosity, there is no innovation.” However, different countries have different ethical norms and boundaries. Whether stem cells may be obtained from human embryos, whether genes that influence intelligence should be studied, are not questions of science only, says the biochemist. “On the one hand, it can be advantageous to, for example, study the influence of genetics on intelligence to perhaps improve the latter.” On the other hand, it is socially controversial, because some people are afraid of discrimination based on genetic differences. “It is not for the scientist to decide; all societal groups in a country should participate in determining the boundaries of science.” Depending on culture and the situation in a country, different decisions will be made regarding, for example, the production of embryonic stem cells. In Israel, surplus human embryos from artificial insemination may be used to obtain stem cells. According to the embryo protection law, German researchers may only import such cell lines (e.g., from Israel), and may not produce them themselves. “Science in Germany is burdened by bureaucracy,” says Ciechanover with a smile. The Germans could learn from Israel to be more flexible. However, the Nobel laureate mentioned that his countrymen could do with better planning. “The right balance lies somewhere in between.” This can only be learned through continuous exchange and cooperation.