Can 100-year-old research lead to the discovery of novel mechanisms of inheritance?

A Groundbreaking Project Will Revisit 120-Year-Old Research to Redefine the Future of Epigenetics

Can 100-Year-Old Research Lead to the Discovery of Novel Mechanisms of Inheritance?

International Team to Reevaluate and Recreate Experiments from Vienna’s Legendary Biologische Versuchsanstalt, Led by TAU’s Prof. Oded Rechavi

In 1902, three prominent Jewish biologists established the Biologische Versuchsanstalt (BVA) in then Austro-Hungarian Vienna. Now, an international team led by Tel Aviv University’s Prof. Oded Rechavi has been awarded a $1.2 million grant by the prestigious Human Frontier Science Program (HFSP) to follow in their footsteps. HFSP is known for its highly competitive selection process, approving only 4% of proposals submitted each year, and indeed the team’s project is truly exceptional, both scientifically and historically.

“We propose a unique study, combining history and cutting-edge biology, focused on the BVA - one of the most groundbreaking institutes of the early 20th century,” says Prof. Rechavi, of the School of Biochemistry, Neurobiology, and Biophysics at the Wise Faculty of Life Sciences, Tel Aviv University. It stood out with a focus on conducting long-term experiments in live animals, a new concept in biological study of those days, and its founders, led by Hans Leo Przibram, emphasized the importance of biology as an empirical and quantitative science on the one hand, and of studying animals in habitats as natural as possible on the other. Przibram led and supported very long experiments in hundreds of species of animals, many of which were never used in research later on or even successfully raised in captivity. The BVA was also innovative with the implementation of advanced methods for climate control, allowing researchers to carefully study the influence of the environment on biology.

“The BVA gained notoriety through Paul Kammerer, who claimed that environmental factors influenced inheritance and was later accused of fraud. However, other respected researchers at the BVA also studied the inheritance of acquired traits—without disproof. Tragically, the scandal and the Nazi persecution of the institute’s Jewish members led to its collapse. As modern genetics emerged, the entire concept of acquired trait inheritance was pushed aside—until recent discoveries in epigenetics brought it back into scientific discourse,” adds Prof. Rechavi.

For nearly a century, the idea of inheriting acquired traits was considered scientific heresy. But in the past 15 years, research in epigenetic inheritance has breathed new life into this controversial topic. Prof. Rechavi characterized a molecular mechanism enabling the transgenerational inheritance of acquired traits in the highly useful model organism, the C. elegans nematode, via small RNA molecules. Now, the next challenge is to demonstrate that similar mechanisms exist across other species - potentially reshaping our understanding of evolution. And this is where the BVA’s historical work becomes newly relevant.

“The papers published by BVA researchers made headlines but were largely ignored because, for a long time, few believed in non-genetic inheritance,” Prof. Rechavi explains. “The question is: can we replicate their experiments using modern tools and knowledge? For example, one of BVA director Hans Przibram’s most promising studies involved growing rats to in warm climate over generations to observe whether the environment can affect their offspring body and tail size. We plan to recreate this experiment as one of our first steps. Today’s improved temperature control systems and the ability to account for genetic variation could allow our team to isolate true epigenetic effects from purely genetic one, potentially validating theories that were ahead of their time more than a century ago.”

International partners

Starting this December, Prof. Oded Rechavi will lead the historical research and assessment of the rich scientific legacy of the BVA, with the support of Prof. Gerd Müller, an expert in the study of the relationship between evolution and development and the editor of a recently published book about the BVA, studying the Viennese sociocultural context at the time of the BVA's founding.

Prof. Katharina Gapp, an expert in the study of environmentally induced traits, their epigenetic underpinnings and inheritance in rodents, will lead the reproduction of Przibram's 1925 rat experiments in rodents of genetically identical background & housed in standardized and temperature-controlled cages and complement these observations with molecular studies on small RNA and the mechanistic underpinnings, aided by the expertise in the Rechavi lab.

Prof. Miguel Vences, an expert in the study of amphibian phylogeny and systematics and patterns and processes of species formation, will lead the reproduction of the salamander experiments conducted in the BVA with the goal of identifying if any of these studies indeed succeeded in demonstrating the inheritance of such environmentally triggered changes.

According to Kammerer, his "experimentum crucis" describing acquired traits inheritance was with a sea squirt (ascidian) called Ciona intestinalis, allegedly demonstrating a transgenerational effect of siphon elongation following amputations. Unfortunately, Kammerer never published his study design, and multiple attempts to reproduce it failed to identify transgenerational effects. Prof. Yasunori Sasakura, a world leader in the study of ascidians as models for developmental genetics and evolution, who was the first to make knockout strains of Ciona intestinalis, will lead the search for molecular mechanisms of epigenetic inheritance in the model organism. C. intestinalis is an organism with large phenotypical diversity in different environmental conditions. Identification of such epigenetic inheritance mechanisms in the ascidian could provide an indication to the validity of the experiments conducted at the BVA without reproducing them precisely.